@article {472, title = {Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits}, journal = {Biological Psychiatry}, volume = {95}, year = {2024}, month = {2024/05/01}, pages = {859 - 869}, abstract = {

BackgroundThe number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta?genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD).BackgroundThe number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta?genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD).

}, isbn = {0006-3223}, doi = {10.1016/j.biopsych.2023.11.025}, author = {Verhoef, Ellen and Allegrini, Andrea G. and Jansen, Philip R. and Lange, Katherine and Wang, Carol A. and Morgan, Angela T. and Ahluwalia, Tarunveer S. and Symeonides, Christos and Andreassen, Ole A. and Bartels, Meike and Boomsma, Dorret and Dale, Philip S. and Ehli, Erik and Fernandez-Orth, Dietmar and Guxens, M{\`o}nica and Hakulinen, Christian and Harris, Kathleen Mullan and Haworth, Simon and de Hoyos, Luc{\'\i}a and Jaddoe, Vincent and Keltikangas-J{\"a}rvinen, Liisa and Lehtim{\"a}ki, Terho and Middeldorp, Christel and Min, Josine L. and Mishra, Pashupati P. and Nj{\o}lstad, P{\r a}l Rasmus and Sunyer, Jordi and Tate, Ashley E. and Timpson, Nicholas and van der Laan, Camiel and Vrijheid, Martine and Vuoksimaa, Eero and Whipp, Alyce and Ystrom, Eivind and ACTION Consortium and Barwon Infant Study investigator group and Eising, Else and Franken, Marie-Christine and Hypponen, Elina and Mansell, Toby and Olislagers, Mitchell and Omerovic, Emina and Rimfeld, Kaili and Schlag, Fenja and Selzam, Saskia and Shapland, Chin Yang and Tiemeier, Henning and Whitehouse, Andrew J.O. and Saffery, Richard and B{\o}nnelykke, Klaus and Reilly, Sheena and Pennell, Craig E. and Wake, Melissa and Cecil, Charlotte A.M. and Plomin, Robert and Fisher, Simon E. and St. Pourcain, Beate} } @article {477, title = {A multi-omics data analysis workflow packaged as a FAIR Digital Object}, journal = {GigaScience}, volume = {13}, year = {2024}, month = {01}, pages = {giad115}, abstract = {

Applying good data management and FAIR (Findable, Accessible, Interoperable, and Reusable) data principles in research projects can help disentangle knowledge discovery, study result reproducibility, and data reuse in future studies. Based on the concepts of the original FAIR principles for research data, FAIR principles for research software were recently proposed. FAIR Digital Objects enable discovery and reuse of Research Objects, including computational workflows for both humans and machines. Practical examples can help promote the adoption of FAIR practices for computational workflows in the research community. We developed a multi-omics data analysis workflow implementing FAIR practices to share it as a FAIR Digital Object.We conducted a case study investigating shared patterns between multi-omics data and childhood externalizing behavior. The analysis workflow was implemented as a modular pipeline in the workflow manager Nextflow, including containers with software dependencies. We adhered to software development practices like version control, documentation, and licensing. Finally, the workflow was described with rich semantic metadata, packaged as a Research Object Crate, and shared via WorkflowHub.Along with the packaged multi-omics data analysis workflow, we share our experiences adopting various FAIR practices and creating a FAIR Digital Object. We hope our experiences can help other researchers who develop omics data analysis workflows to turn FAIR principles into practice.

}, issn = {2047-217X}, doi = {10.1093/gigascience/giad115}, url = {https://doi.org/10.1093/gigascience/giad115}, author = {Niehues, Anna and de~Visser, Casper and Hagenbeek, Fiona A and Kulkarni, Purva and Pool, Ren{\'e} and Karu, Naama and Kindt, Alida S D and Singh, Gurnoor and Vermeiren, Robert R J M and Boomsma, Dorret I and van~Dongen, Jenny and {\textquoteright}t~Hoen, Peter A C and van~Gool, Alain J} } @article {468, title = {Beyond the global brain differences: Intra-individual variability differences in 1q21.1 distal and 15q11.2 {BP1-BP2} deletion carriers}, journal = {Biological Psychiatry}, year = {2023}, abstract = {

BACKGROUND: The 1q21.1 distal and 15q11.2 BP1-BP2 CNVs exhibit regional and global brain differences compared to non-carriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intra-individual variability measures can be used to test for regional differences beyond global differences in brain structure.

METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n=30) and duplication (n=27), and 15q11.2 BP1-BP2 deletion (n=170) and duplication (n=243) carriers and matched non-carriers (n=2,350). Regional intra-deviation (RID) scores i.e., the standardized difference between an individual\&$\#$39;s regional difference and global difference, were used to test for regional differences that diverge from the global difference.

RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate and temporal pole differed less, and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex and temporal pole differed less, and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.

CONCLUSION: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 CNVs. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 CNVs, with the potential to increase our understanding of mechanisms involved in altered neurodevelopment.

}, keywords = {15q11.2 BP1-BP2, 1q21.1 distal, brain structure, copy number variants, intra-individual variability, magnetic resonance imaging}, doi = {10.1016/j.biopsych.2023.08.018}, author = {Boen, Rune and Kaufmann, Tobias and van der Meer, Dennis and Frei, Oleksandr and Agartz, Ingrid and Ames, David and Andersson, Micael and Armstrong, Nicola J and Artiges, Eric and Atkins, Joshua R and Bauer, Jochen and Benedetti, Francesco and Boomsma, Dorret I and Brodaty, Henry and Brosch, Katharina and Buckner, Randy L and Cairns, Murray J and Calhoun, Vince and Caspers, Svenja and Cichon, Sven and Corvin, Aiden P and Facorro, Benedicto Crespo and Dannlowski, Udo and David, Friederike S and de Geus, Eco J C and de Zubicaray, Greig I and Desrivieres, Sylvane and Doherty, Joanne L and Donohoe, Gary and Ehrlich, Stefan and Eising, Else and Espeseth, Thomas and Fisher, Simon E and Forstner, Andreas J and Uy{\`a}, Lidia Fortaner and Frouin, Vincent and Fukunaga, Masaki and Ge, Tian and Glahn, David C and Goltermann, Janik and Grabe, Hans J and Green, Melissa J and Groenewold, Nynke A and Grotegerd, Dominik and Hahn, Tim and Hashimoto, Ryota and Hehir-Kwa, Jayne Y and Henskens, Frans A and Holmes, Avram J and Haberg, Asta K and Haavik, Jan and Jacquemont, S{\'e}bastien and Jansen, Andreas and Jockwitz, Christiane and J{\"o}nsson, Erik G and Kikuchi, Masataka and Kircher, Tilo and Kumar, Kuldeep and Le Hellard, Stephanie and Leu, Costin and Linden, David E and Liu, Jingyu and Loughnan, Robert and Mather, Karen A and McMahon, Katie L and McRae, Allan F and Medland, Sarah E and Meinert, Susanne and Moreau, Clara A and Morris, Derek W and Mowry, Bryan J and M{\"u}hleisen, Thomas W and Nenadi{\'c}, Igor and N{\"o}then, Markus M and Nyberg, Lars and Owen, Michael J and Paolini, Marco and Paus, Tomas and Pausova, Zdenka and Persson, Karin and Quid{\'e}, Yann and Marques, Tiago Reis and Sachdev, Perminder S and Sando, Sigrid B and Schall, Ulrich and Scott, Rodney J and Selb{\ae}k, Geir and Shumskaya, Elena and Silva, Ana I and Sisodiya, Sanjay M and Stein, Frederike and Stein, Dan J and Straube, Benjamin and Streit, Fabian and Strike, Lachlan T and Teumer, Alexander and Teutenberg, Lea and Thalamuthu, Anbupalam and Tooney, Paul A and Tordesillas-Guti{\'e}rrez, Diana and Trollor, Julian N and Ent, Dennis van {\textquoteright}t and van den Bree, Marianne B M and van Haren, Neeltje E M and Vazquez-Bourgon, Javier and V{\"o}lzke, Henry and Wen, Wei and Wittfeld, Katharina and Ching, Christopher R K and Westlye, Lars T and Thompson, Paul M and Bearden, Carrie E and Selmer, Kaja K and Aln{\ae}s, Dag and Andreassen, Ole A and Sonderby, Ida E} } @inbook {458, title = {Chapter 32 - Twins and omics: the role of twin studies in multi-omics}, booktitle = {Twin Research for Everyone}, year = {2022}, pages = {547-584}, publisher = {Academic Press}, organization = {Academic Press}, abstract = {

Genomics, transcriptomics, proteomics, and metabolomics are the four main omics domains, referring to high-throughput studies of the genome (DNA), transcriptome (RNA), proteome (proteins), and metabolome (metabolites). Together, these omics domains describe how proteins are formed by the transcription and translation of genetic information and how cells, tissues, and organisms\’ function at the molecular level. Other omics layers reflect regulatory and modulatory processes or exposures to the environment. Twin designs offer powerful analytical tools to study variation in omics data and the influence of omics on phenotypes and phenotypic development. Here, we review and discuss the contribution of twin studies to omics and argue that twin research plays a valuable role in omics research.

}, keywords = {epigenome, Genome, Metabolome, Omics, Transcriptome, Twin design, twins}, isbn = {978-0-12-821514-2}, doi = {https://doi.org/10.1016/B978-0-12-821514-2.00029-5}, url = {https://www.sciencedirect.com/science/article/pii/B9780128215142000295}, author = {Fiona A. Hagenbeek and Jenny van Dongen and Ren{\'e} Pool and Dorret I. Boomsma}, editor = {Adam Tarnoki and David Tarnoki and Jennifer Harris and Nancy Segal} } @article {448, title = {Discovery of 42 genome-wide significant loci associated with dyslexia}, journal = {Nature Genetics}, volume = {54}, year = {2022}, pages = {1621{\textendash}1629}, abstract = {

Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70\%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6\% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.

}, doi = {10.1038/s41588-022-01192-y}, author = {Doust, Catherine and Fontanillas, Pierre and Eising, Else and Gordon, Scott D and Wang, Zhengjun and Alag{\"o}z, G{\"o}kberk and Molz, Barbara and 23andMe Research Team and Quantitative Trait Working Group of the GenLang Consortium and Pourcain, Beate St and Francks, Clyde and Marioni, Riccardo E and Zhao, Jingjing and Paracchini, Silvia and Talcott, Joel B and Monaco, Anthony P and Stein, John F and Gruen, Jeffrey R and Olson, Richard K and Willcutt, Erik G and DeFries, John C and Pennington, Bruce F and Smith, Shelley D and Wright, Margaret J and Martin, Nicholas G and Auton, Adam and Bates, Timothy C and Fisher, Simon E and Luciano, Michelle} } @article {463, title = {DNA methylation in peripheral tissues and left-handedness}, journal = {Scientific Reports}, volume = {12}, year = {2022}, pages = {5606}, abstract = {

Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study of left-handedness. In a meta-analysis of 3914 adults of whole-blood DNA methylation, we observed that CpG sites located in proximity of handedness-associated genetic variants were more strongly associated with left-handedness than other CpG sites (P = 0.04), but did not identify any differentially methylated positions. In longitudinal analyses of DNA methylation in peripheral blood and buccal cells from children (N = 1737), we observed moderately stable associations across age (correlation range [0.355-0.578]), but inconsistent across tissues (correlation range [- 0.384 to 0.318]). We conclude that DNA methylation in peripheral tissues captures little of the variance in handedness. Future investigations should consider other more targeted sources of tissue, such as the brain.

}, doi = {10.1038/s41598-022-08998-0}, author = {Odintsova, Veronika V and Suderman, Matthew and Hagenbeek, Fiona A and Caramaschi, Doretta and Hottenga, Jouke-Jan and Pool, Ren{\'e} and BIOS Consortium and Dolan, Conor V and Ligthart, Lannie and van Beijsterveldt, Catharina E M and Willemsen, Gonneke and de Geus, Eco J C and Beck, Jeffrey J and Ehli, Erik A and Cuellar-Partida, Gabriel and Evans, David M and Medland, Sarah E and Relton, Caroline L and Boomsma, Dorret I and van Dongen, Jenny} } @article {459, title = {Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people}, journal = {Proceedings of the National Academy of Sciences (PNAS)}, volume = {119}, year = {2022}, pages = {e2202764119}, abstract = {

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80\% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 \× 10\−8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26\% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.

}, keywords = {genome-wide association study, language, meta-analysis, reading}, doi = {10.1073/pnas.2202764119}, author = {Eising, Else and Mirza-Schreiber, Nazanin and de Zeeuw, Eveline L and Wang, Carol A and Truong, Dongnhu T and Allegrini, Andrea G and Shapland, Chin Yang and Zhu, Gu and Wigg, Karen G and Gerritse, Margot L and Molz, Barbara and Alag{\"o}z, G{\"o}kberk and Gialluisi, Alessandro and Abbondanza, Filippo and Rimfeld, Kaili and van Donkelaar, Marjolein and Liao, Zhijie and Jansen, Philip R and Andlauer, Till F M and Bates, Timothy C and Bernard, Manon and Blokland, Kirsten and Bonte, Milene and B{\o}rglum, Anders D and Bourgeron, Thomas and Brandeis, Daniel and Ceroni, Fabiola and Cs{\'e}pe, Val{\'e}ria and Dale, Philip S and de Jong, Peter F and DeFries, John C and D{\'e}monet, Jean-Fran\c cois and Demontis, Ditte and Feng, Yu and Gordon, Scott D and Guger, Sharon L and Hayiou-Thomas, Marianna E and Hern{\'a}ndez-Cabrera, Juan A and Hottenga, Jouke-Jan and Hulme, Charles and Kere, Juha and Kerr, Elizabeth N and Koomar, Tanner and Landerl, Karin and Leonard, Gabriel T and Lovett, Maureen W and Lyytinen, Heikki and Martin, Nicholas G and Martinelli, Angela and Maurer, Urs and Michaelson, Jacob J and Moll, Kristina and Monaco, Anthony P and Morgan, Angela T and N{\"o}then, Markus M and Pausova, Zdenka and Pennell, Craig E and Pennington, Bruce F and Price, Kaitlyn M and Rajagopal, Veera M and Ramus, Franck and Richer, Louis and Simpson, Nuala H and Smith, Shelley D and Snowling, Margaret J and Stein, John and Strug, Lisa J and Talcott, Joel B and Tiemeier, Henning and van der Schroeff, Marc P and Verhoef, Ellen and Watkins, Kate E and Wilkinson, Margaret and Wright, Margaret J and Barr, Cathy L and Boomsma, Dorret I and Carreiras, Manuel and Franken, Marie-Christine J and Gruen, Jeffrey R and Luciano, Michelle and M{\"u}ller-Myhsok, Bertram and Newbury, Dianne F and Olson, Richard K and Paracchini, Silvia and Paus, Tom{\'a}\v s and Plomin, Robert and Reilly, Sheena and Schulte-K{\"o}rne, Gerd and Tomblin, J Bruce and van Bergen, Elsje and Whitehouse, Andrew J O and Willcutt, Erik G and St Pourcain, Beate and Francks, Clyde and Fisher, Simon E} } @article {469, title = {Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention}, journal = {Nature Genetics}, volume = {54}, year = {2022}, pages = {1332{\textendash}1344}, abstract = {

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

}, doi = {10.1038/s41588-022-01165-1}, author = {Wang, Zhe and Emmerich, Andrew and Pillon, Nicolas J and Moore, Tim and Hemerich, Daiane and Cornelis, Marilyn C and Mazzaferro, Eugenia and Broos, Siacia and Ahluwalia, Tarunveer S and Bartz, Traci M and Bentley, Amy R and Bielak, Lawrence F and Chong, Mike and Chu, Audrey Y and Berry, Diane and Dorajoo, Rajkumar and Dueker, Nicole D and Kasbohm, Elisa and Feenstra, Bjarke and Feitosa, Mary F and Gieger, Christian and Graff, Mariaelisa and Hall, Leanne M and Haller, Toomas and Hartwig, Fernando P and Hillis, David A and Huikari, Ville and Heard-Costa, Nancy and Holzapfel, Christina and Jackson, Anne U and Johansson, \AAsa and J{\o}rgensen, Anja Moltke and Kaakinen, Marika A and Karlsson, Robert and Kerr, Kathleen F and Kim, Boram and Koolhaas, Chantal M and Kutalik, Zoltan and Lagou, Vasiliki and Lind, Penelope A and Lorentzon, Mattias and Lyytik{\"a}inen, Leo-Pekka and Mangino, Massimo and Metzendorf, Christoph and Monroe, Kristine R and Pacolet, Alexander and P{\'e}russe, Louis and Pool, Ren{\'e} and Richmond, Rebecca C and Rivera, Natalia V and Robiou-du-Pont, Sebastien and Schraut, Katharina E and Schulz, Christina-Alexandra and Stringham, Heather M and Tanaka, Toshiko and Teumer, Alexander and Turman, Constance and van der Most, Peter J and Vanmunster, Mathias and van Rooij, Frank J A and van Vliet-Ostaptchouk, Jana V and Zhang, Xiaoshuai and Zhao, Jing-Hua and Zhao, Wei and Balkhiyarova, Zhanna and Balslev-Harder, Marie N and Baumeister, Sebastian E and Beilby, John and Blangero, John and Boomsma, Dorret I and Brage, Soren and Braund, Peter S and Brody, Jennifer A and Bruinenberg, Marcel and Ekelund, Ulf and Liu, Ching-Ti and Cole, John W and Collins, Francis S and Cupples, L Adrienne and Esko, T{\~o}nu and Enroth, Stefan and Faul, Jessica D and Fernandez-Rhodes, Lindsay and Fohner, Alison E and Franco, Oscar H and Galesloot, Tessel E and Gordon, Scott D and Grarup, Niels and Hartman, Catharina A and Heiss, Gerardo and Hui, Jennie and Illig, Thomas and Jago, Russell and James, Alan and Joshi, Peter K and Jung, Taeyeong and K{\"a}h{\"o}nen, Mika and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Kolcic, Ivana and Kraft, Peter P and Kuusisto, Johanna and Launer, Lenore J and Li, Aihua and Linneberg, Allan and Luan, Jian{\textquoteright}an and Vidal, Pedro Marques and Medland, Sarah E and Milaneschi, Yuri and Moscati, Arden and Musk, Bill and Nelson, Christopher P and Nolte, Ilja M and Pedersen, Nancy L and Peters, Annette and Peyser, Patricia A and Power, Christine and Raitakari, Olli T and Reedik, M{\"a}gi and Reiner, Alex P and Ridker, Paul M and Rudan, Igor and Ryan, Kathy and Sarzynski, Mark A and Scott, Laura J and Scott, Robert A and Sidney, Stephen and Siggeirsdottir, Kristin and Smith, Albert V and Smith, Jennifer A and Sonestedt, Emily and Str{\o}m, Marin and Tai, E Shyong and Teo, Koon K and Thorand, Barbara and T{\"o}njes, Anke and Tremblay, Angelo and Uitterlinden, Andre G and Vangipurapu, Jagadish and van Schoor, Natasja and V{\"o}lker, Uwe and Willemsen, Gonneke and Williams, Kayleen and Wong, Quenna and Xu, Huichun and Young, Kristin L and Yuan, Jian Min and Zillikens, M Carola and Zonderman, Alan B and Ameur, Adam and Bandinelli, Stefania and Bis, Joshua C and Boehnke, Michael and Bouchard, Claude and Chasman, Daniel I and Smith, George Davey and de Geus, Eco J C and Deldicque, Louise and D{\"o}rr, Marcus and Evans, Michele K and Ferrucci, Luigi and Fornage, Myriam and Fox, Caroline and Garland, Jr, Theodore and Gudnason, Vilmundur and Gyllensten, Ulf and Hansen, Torben and Hayward, Caroline and Horta, Bernardo L and Hypponen, Elina and Jarvelin, Marjo-Riitta and Johnson, W Craig and Kardia, Sharon L R and Kiemeney, Lambertus A and Laakso, Markku and Langenberg, Claudia and Lehtim{\"a}ki, Terho and Marchand, Loic Le and Lifelines Cohort Study and Magnusson, Patrik K E and Martin, Nicholas G and Melbye, Mads and Metspalu, Andres and Meyre, David and North, Kari E and Ohlsson, Claes and Oldehinkel, Albertine J and Orho-Melander, Marju and Pare, Guillaume and Park, Taesung and Pedersen, Oluf and Penninx, Brenda W J H and Pers, Tune H and Polasek, Ozren and Prokopenko, Inga and Rotimi, Charles N and Samani, Nilesh J and Sim, Xueling and Snieder, Harold and S{\o}rensen, Thorkild I A and Spector, Tim D and Timpson, Nicholas J and van Dam, Rob M and van der Velde, Nathalie and van Duijn, Cornelia M and Vollenweider, Peter and V{\"o}lzke, Henry and Voortman, Trudy and Waeber, G{\'e}rard and Wareham, Nicholas J and Weir, David R and Wichmann, Heinz-Erich and Wilson, James F and Hevener, Andrea L and Krook, Anna and Zierath, Juleen R and Thomis, Martine A I and Loos, Ruth J F and Hoed, Marcel den} } @article {460, title = {Genome-wide association meta-analysis identifies 29 new acne susceptibility loci}, journal = {Nature Communications}, volume = {13}, year = {2022}, pages = {702}, abstract = {

Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6\% of the variance in acne liability in an independent cohort.

}, doi = {10.1038/s41467-022-28252-5}, author = {Mitchell, Brittany L and Saklatvala, Jake R and Dand, Nick and Hagenbeek, Fiona A and Li, Xin and Min, Josine L and Thomas, Laurent and Bartels, Meike and Jan Hottenga, Jouke and Lupton, Michelle K and Boomsma, Dorret I and Dong, Xianjun and Hveem, Kristian and L{\o}set, Mari and Martin, Nicholas G and Barker, Jonathan N and Han, Jiali and Smith, Catherine H and Renter{\'\i}a, Miguel E and Simpson, Michael A} } @article {455, title = {Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms}, journal = {Journal of the American Academy of Child \& Adolescent Psychiatry}, volume = {61}, year = {2022}, pages = {934{\textendash}945}, abstract = {

OBJECTIVE: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence.

METHOD: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.

RESULTS: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66\%, 95\% CI = 0.84-2.48

}, keywords = {anxiety, Depression, genetic epidemiology, molecular genetics, repeated measures}, doi = {10.1016/j.jaac.2021.11.035}, author = {Jami, Eshim S and Hammerschlag, Anke R and Ip, Hill F and Allegrini, Andrea G and Benyamin, Beben and Border, Richard and Diemer, Elizabeth W and Jiang, Chang and Karhunen, Ville and Lu, Yi and Lu, Qing and Mallard, Travis T and Mishra, Pashupati P and Nolte, Ilja M and Palviainen, Teemu and Peterson, Roseann E and Sallis, Hannah M and Shabalin, Andrey A and Tate, Ashley E and Thiering, Elisabeth and Vilor-Tejedor, Nat{\`a}lia and Wang, Carol and Zhou, Ang and Adkins, Daniel E and Alemany, Silvia and Ask, Helga and Chen, Qi and Corley, Robin P and Ehli, Erik A and Evans, Luke M and Havdahl, Alexandra and Hagenbeek, Fiona A and Hakulinen, Christian and Henders, Anjali K and Hottenga, Jouke Jan and Korhonen, Tellervo and Mamun, Abdullah and Marrington, Shelby and Neumann, Alexander and Rimfeld, Kaili and Rivadeneira, Fernando and Silberg, Judy L and van Beijsterveldt, Catharina E and Vuoksimaa, Eero and Whipp, Alyce M and Tong, Xiaoran and Andreassen, Ole A and Boomsma, Dorret I and Brown, Sandra A and Burt, S Alexandra and Copeland, William and Dick, Danielle M and Harden, K Paige and Harris, Kathleen Mullan and Hartman, Catharina A and Heinrich, Joachim and Hewitt, John K and Hopfer, Christian and Hypponen, Elina and Jarvelin, Marjo-Riitta and Kaprio, Jaakko and Keltikangas-J{\"a}rvinen, Liisa and Klump, Kelly L and Krauter, Kenneth and Kuja-Halkola, Ralf and Larsson, Henrik and Lehtim{\"a}ki, Terho and Lichtenstein, Paul and Lundstr{\"o}m, Sebastian and Maes, Hermine H and Magnus, Per and Munaf{\`o}, Marcus R and Najman, Jake M and Nj{\o}lstad, P\aal R and Oldehinkel, Albertine J and Pennell, Craig E and Plomin, Robert and Reichborn-Kjennerud, Ted and Reynolds, Chandra and Rose, Richard J and Smolen, Andrew and Snieder, Harold and Stallings, Michael and Standl, Marie and Sunyer, Jordi and Tiemeier, Henning and Wadsworth, Sally J and Wall, Tamara L and Whitehouse, Andrew J O and Williams, Gail M and Ystr{\o}m, Eivind and Nivard, Michel G and Bartels, Meike and Middeldorp, Christel M} } @article {462, title = {Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities}, journal = {Translational Psychiatry}, volume = {12}, year = {2022}, pages = {495}, abstract = {

Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)\–GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n\ =\ 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p~1.45\ \×\ 10\–2, threshold = 2.5\ \×\ 10\–2). For the GenLang Cohort (n\ =\ 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q\ =\ 1.02\ \×\ 10\–2). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n\ =\ 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q\ \<\ 9.00\ \×\ 10\–4). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations.

}, doi = {10.1038/s41398-022-02250-z}, author = {Price, Kaitlyn M and Wigg, Karen G and Eising, Else and Feng, Yu and Blokland, Kirsten and Wilkinson, Margaret and Kerr, Elizabeth N and Guger, Sharon L and Quantitative Trait Working Group of the GenLang Consortium and Fisher, Simon E and Lovett, Maureen W and Strug, Lisa J and Barr, Cathy L} } @article {461, title = {Item-level genome-wide association study of the Alcohol Use Disorders Identification Test in three population-based cohorts}, journal = {The American Journal of Psychiatry}, volume = {179}, year = {2022}, pages = {58{\textendash}70}, abstract = {

OBJECTIVE: Genome-wide association studies (GWASs) of the Alcohol Use Disorders Identification Test (AUDIT), a 10-item screen for alcohol use disorder (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which may have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders and/or medical conditions. The authors used genomic structural equation modeling to elucidate the genetics of alcohol consumption and problematic consequences of alcohol use as measured by AUDIT.

METHODS: To explore these unexpected differences in genetic correlations, the authors conducted the first item-level and the largest GWAS of AUDIT items (N=160,824) and applied a multivariate framework to mitigate previous biases.

RESULTS: The authors identified novel patterns of similarity (and dissimilarity) among the AUDIT items and found evidence of a correlated two-factor structure at the genetic level ({\textquoteleft}{\textquoteleft}consumption\&$\#$39;\&$\#$39; and {\textquoteleft}{\textquoteleft}problems,\&$\#$39;\&$\#$39; rg=0.80). Moreover, by applying empirically derived weights to each of the AUDIT items, the authors constructed an aggregate measure of alcohol consumption that was strongly associated with alcohol dependence (rg=0.67), moderately associated with several other psychiatric disorders, and no longer positively associated with health and positive socioeconomic outcomes. Lastly, by conducting polygenic analyses in three independent cohorts that differed in their ascertainment and prevalence of AUD, the authors identified novel genetic associations between alcohol consumption, alcohol misuse, and health.

CONCLUSIONS: This work further emphasizes the value of AUDIT for both clinical and genetic studies of AUD and the importance of using multivariate methods to study genetic associations that are more closely related to AUD.

}, keywords = {Alcohol, Alcohol Consumption, ALSPAC, Genomic Structural Equation Modeling, GWAS, Substance-Related and Addictive Disorders}, doi = {10.1176/appi.ajp.2020.20091390}, author = {Mallard, Travis T and Savage, Jeanne E and Johnson, Emma C and Huang, Yuye and Edwards, Alexis C and Hottenga, Jouke J and Grotzinger, Andrew D and Gustavson, Daniel E and Jennings, Mariela V and Anokhin, Andrey and Dick, Danielle M and Edenberg, Howard J and Kramer, John R and Lai, Dongbing and Meyers, Jacquelyn L and Pandey, Ashwini K and Harden, Kathryn Paige and Nivard, Michel G and de Geus, Eco J C and Boomsma, Dorret I and Agrawal, Arpana and Davis, Lea K and Clarke, Toni-Kim and Palmer, Abraham A and Sanchez-Roige, Sandra} } @article {465, title = {Overview of CAPICE - Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe - an EU Marie Sk{\l}odowska-Curie International Training Network}, journal = {European Child \& Adolescent Psychiatry}, volume = {31}, year = {2022}, pages = {829{\textendash}839}, abstract = {

The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).

}, keywords = {anxiety, Attention deficit hyperactivity disorder (ADHD), Childhood and adolescence psychopathology, Depression, Psychiatric genetics}, doi = {10.1007/s00787-020-01713-2}, author = {Rajula, Hema Sekhar Reddy and Manchia, Mirko and Agarwal, Kratika and Akingbuwa, Wonuola A and Allegrini, Andrea G and Diemer, Elizabeth and Doering, Sabrina and Haan, Elis and Jami, Eshim S and Karhunen, Ville and Leone, Marica and Schellhas, Laura and Thompson, Ashley and van den Berg, St{\'e}phanie M and Bergen, Sarah E and Kuja-Halkola, Ralf and Hammerschlag, Anke R and J{\"a}rvelin, Marjo Riitta and Leval, Amy and Lichtenstein, Paul and Lundstr{\"o}m, Sebastian and Mauri, Matteo and Munaf{\`o}, Marcus R and Myers, David and Plomin, Robert and Rimfeld, Kaili and Tiemeier, Henning and Ystrom, Eivind and Fanos, Vassilios and Bartels, Meike and Middeldorp, Christel M} } @article {454, title = {1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans}, journal = {Translational Psychiatry}, volume = {11}, year = {2021}, pages = {182}, abstract = {

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48\% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

}, doi = { 10.1038/s41398-021-01213-0}, author = {S{\o}nderby, Ida E and van der Meer, Dennis and Moreau, Clara and Kaufmann, Tobias and Walters, G Bragi and Ellegaard, Maria and Abdellaoui, Abdel and Ames, David and Amunts, Katrin and Andersson, Micael and Armstrong, Nicola J and Bernard, Manon and Blackburn, Nicholas B and Blangero, John and Boomsma, Dorret I and Brodaty, Henry and Brouwer, Rachel M and B{\"u}low, Robin and B{\o}en, Rune and Cahn, Wiepke and Calhoun, Vince D and Caspers, Svenja and Ching, Christopher R K and Cichon, Sven and Ciufolini, Simone and Crespo-Facorro, Benedicto and Curran, Joanne E and Dale, Anders M and Dalvie, Shareefa and Dazzan, Paola and de Geus, Eco J C and de Zubicaray, Greig I and de Zwarte, Sonja M C and Desrivieres, Sylvane and Doherty, Joanne L and Donohoe, Gary and Draganski, Bogdan and Ehrlich, Stefan and Eising, Else and Espeseth, Thomas and Fejgin, Kim and Fisher, Simon E and Fladby, Tormod and Frei, Oleksandr and Frouin, Vincent and Fukunaga, Masaki and Gareau, Thomas and Ge, Tian and Glahn, David C and Grabe, Hans J and Groenewold, Nynke A and G{\'u}stafsson, {\'O}mar and Haavik, Jan and Haberg, Asta K and Hall, Jeremy and Hashimoto, Ryota and Hehir-Kwa, Jayne Y and Hibar, Derrek P and Hillegers, Manon H J and Hoffmann, Per and Holleran, Laurena and Holmes, Avram J and Homuth, Georg and Hottenga, Jouke-Jan and Hulshoff Pol, Hilleke E and Ikeda, Masashi and Jahanshad, Neda and Jockwitz, Christiane and Johansson, Stefan and J{\"o}nsson, Erik G and J{\o}rgensen, Niklas R and Kikuchi, Masataka and Knowles, Emma E M and Kumar, Kuldeep and Le Hellard, Stephanie and Leu, Costin and Linden, David E J and Liu, Jingyu and Lundervold, Arvid and Lundervold, Astri Johansen and Maillard, Anne M and Martin, Nicholas G and Martin-Brevet, Sandra and Mather, Karen A and Mathias, Samuel R and McMahon, Katie L and McRae, Allan F and Medland, Sarah E and Meyer-Lindenberg, Andreas and Moberget, Torgeir and Modenato, Claudia and S{\'a}nchez, Jennifer Monereo and Morris, Derek W and M{\"u}hleisen, Thomas W and Murray, Robin M and Nielsen, Jacob and Nordvik, Jan E and Nyberg, Lars and Loohuis, Loes M Olde and Ophoff, Roel A and Owen, Michael J and Paus, Tomas and Pausova, Zdenka and Peralta, Juan M and Pike, G Bruce and Prieto, Carlos and Quinlan, Erin B and Reinbold, C{\'e}line S and Marques, Tiago Reis and Rucker, James J H and Sachdev, Perminder S and Sando, Sigrid B and Schofield, Peter R and Schork, Andrew J and Schumann, Gunter and Shin, Jean and Shumskaya, Elena and Silva, Ana I and Sisodiya, Sanjay M and Steen, Vidar M and Stein, Dan J and Strike, Lachlan T and Suzuki, Ikuo K and Tamnes, Christian K and Teumer, Alexander and Thalamuthu, Anbupalam and Tordesillas-Guti{\'e}rrez, Diana and Uhlmann, Anne and Ulfarsson, Magnus O and van {\textquoteright}t Ent, Dennis and van den Bree, Marianne B M and Vanderhaeghen, Pierre and Vassos, Evangelos and Wen, Wei and Wittfeld, Katharina and Wright, Margaret J and Agartz, Ingrid and Djurovic, Srdjan and Westlye, Lars T and Stefansson, Hreinn and Stefansson, Kari and Jacquemont, S{\'e}bastien and Thompson, Paul M and Andreassen, Ole A and ENIGMA-CNV working group} } @article {439, title = {DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan}, journal = {Molecular Psychiatry}, volume = {26}, year = {2021}, pages = {2148{\textendash}2162}, abstract = {

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 $\times$ 10-7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83\% of these sites showed the same direction of association with childhood aggression (r = 0.7

}, doi = {10.1038/s41380-020-00987-x}, author = {van Dongen, Jenny and Hagenbeek, Fiona A and Suderman, Matthew and Roetman, Peter J and Sugden, Karen and Chiocchetti, Andreas G and Ismail, Khadeeja and Mulder, Rosa H and Hafferty, Jonathan D and Adams, Mark J and Walker, Rosie M and Morris, Stewart W and Lahti, Jari and K{\"u}pers, Leanne K and Escaramis, Georgia and Alemany, Silvia and Jan Bonder, Marc and Meijer, Mandy and Ip, Hill F and Jansen, Rick and Baselmans, Bart M L and Parmar, Priyanka and Lowry, Estelle and Streit, Fabian and Sirignano, Lea and Send, Tabea S and Frank, Josef and Jylh{\"a}v{\"a}, Juulia and Wang, Yunzhang and Mishra, Pashupati Prasad and Colins, Olivier F and Corcoran, David L and Poulton, Richie and Mill, Jonathan and Hannon, Eilis and Arseneault, Louise and Korhonen, Tellervo and Vuoksimaa, Eero and Felix, Janine F and Bakermans-Kranenburg, Marian J and Campbell, Archie and Czamara, Darina and Binder, Elisabeth and Corpeleijn, Eva and Gonzalez, Juan R and Grazuleviciene, Regina and Gutzkow, Kristine B and Evandt, Jorunn and Vafeiadi, Marina and Klein, Marieke and van der Meer, Dennis and Ligthart, Lannie and BIOS Consortium and Kluft, Cornelis and Davies, Gareth E and Hakulinen, Christian and Keltikangas-J{\"a}rvinen, Liisa and Franke, Barbara and Freitag, Christine M and Konrad, Kerstin and Hervas, Amaia and Fern{\'a}ndez-Rivas, Aranzazu and Vetro, Agnes and Raitakari, Olli and Lehtim{\"a}ki, Terho and Vermeiren, Robert and Strandberg, Timo and R{\"a}ikk{\"o}nen, Katri and Snieder, Harold and Witt, Stephanie H and Deuschle, Michael and Pedersen, Nancy L and H{\"a}gg, Sara and Sunyer, Jordi and Franke, Lude and Kaprio, Jaakko and Ollikainen, Miina and Moffitt, Terrie E and Tiemeier, Henning and van IJzendoorn, Marinus H and Relton, Caroline and Vrijheid, Martine and Sebert, Sylvain and Jarvelin, Marjo-Riitta and Caspi, Avshalom and Evans, Kathryn L and McIntosh, Andrew M and Bartels, Meike and Boomsma, Dorret I} } @article {437, title = {Genetic association study of childhood aggression across raters, instruments, and age}, journal = {Translational Psychiatry}, volume = {11}, year = {2021}, pages = {413}, abstract = {

Childhood aggressive behavior (AGG) has a substantial heritability of around 50\%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31\% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44\%) and in retrospectively assessed childhood aggression (variance explained = 0.20\%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = \ -0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

}, doi = {10.1038/s41398-021-01480-x}, author = {Ip, Hill F and Van der Laan, Camiel M and Krapohl, Eva M L and Brikell, Isabell and S{\'a}nchez-Mora, Cristina and Nolte, Ilja M and St Pourcain, Beate and Bolhuis, Koen and Palviainen, Teemu and Zafarmand, Hadi and Colodro-Conde, Luc{\'\i}a and Gordon, Scott and Zayats, Tetyana and Aliev, Fazil and Jiang, Chang and Wang, Carol A and Saunders, Gretchen and Karhunen, Ville and Hammerschlag, Anke R and Adkins, Daniel E and Border, Richard and Peterson, Roseann E and Prinz, Joseph A and Thiering, Elisabeth and Sepp{\"a}l{\"a}, Ilkka and Vilor-Tejedor, Nat{\`a}lia and Ahluwalia, Tarunveer S and Day, Felix R and Hottenga, Jouke-Jan and Allegrini, Andrea G and Rimfeld, Kaili and Chen, Qi and Lu, Yi and Martin, Joanna and Soler Artigas, Mar{\'\i}a and Rovira, Paula and Bosch, Rosa and Espa{\~n}ol, Gemma and Ramos Quiroga, Josep Antoni and Neumann, Alexander and Ensink, Judith and Grasby, Katrina and Morosoli, Jos{\'e} J and Tong, Xiaoran and Marrington, Shelby and Middeldorp, Christel and Scott, James G and Vinkhuyzen, Anna and Shabalin, Andrey A and Corley, Robin and Evans, Luke M and Sugden, Karen and Alemany, Silvia and Sass, L{\ae}rke and Vinding, Rebecca and Ruth, Kate and Tyrrell, Jess and Davies, Gareth E and Ehli, Erik A and Hagenbeek, Fiona A and de Zeeuw, Eveline and van Beijsterveldt, Toos C E M and Larsson, Henrik and Snieder, Harold and Verhulst, Frank C and Amin, Najaf and Whipp, Alyce M and Korhonen, Tellervo and Vuoksimaa, Eero and Rose, Richard J and Uitterlinden, Andre G and Heath, Andrew C and Madden, Pamela and Haavik, Jan and Harris, Jennifer R and Helgeland, {\O}yvind and Johansson, Stefan and Knudsen, Gun Peggy S and Njolstad, Pal Rasmus and Lu, Qing and Rodriguez, Alina and Henders, Anjali K and Mamun, Abdullah and Najman, Jackob M and Brown, Sandy and Hopfer, Christian and Krauter, Kenneth and Reynolds, Chandra and Smolen, Andrew and Stallings, Michael and Wadsworth, Sally and Wall, Tamara L and Silberg, Judy L and Miller, Allison and Keltikangas-J{\"a}rvinen, Liisa and Hakulinen, Christian and Pulkki-R\aaback, Laura and Havdahl, Alexandra and Magnus, Per and Raitakari, Olli T and Perry, John R B and Llop, Sabrina and Lopez-Espinosa, Maria-Jose and B{\o}nnelykke, Klaus and Bisgaard, Hans and Sunyer, Jordi and Lehtim{\"a}ki, Terho and Arseneault, Louise and Standl, Marie and Heinrich, Joachim and Boden, Joseph and Pearson, John and Horwood, L John and Kennedy, Martin and Poulton, Richie and Eaves, Lindon J and Maes, Hermine H and Hewitt, John and Copeland, William E and Costello, Elizabeth J and Williams, Gail M and Wray, Naomi and Jarvelin, Marjo-Riitta and McGue, Matt and Iacono, William and Caspi, Avshalom and Moffitt, Terrie E and Whitehouse, Andrew and Pennell, Craig E and Klump, Kelly L and Burt, S Alexandra and Dick, Danielle M and Reichborn-Kjennerud, Ted and Martin, Nicholas G and Medland, Sarah E and Vrijkotte, Tanja and Kaprio, Jaakko and Tiemeier, Henning and Davey Smith, George and Hartman, Catharina A and Oldehinkel, Albertine J and Casas, Miquel and Ribas{\'e}s, Marta and Lichtenstein, Paul and Lundstr{\"o}m, Sebastian and Plomin, Robert and Bartels, Meike and Nivard, Michel G and Boomsma, Dorret I} } @article {440, title = {Identical twins carry a persistent epigenetic signature of early genome programming}, journal = {Nature Communications}, volume = {12}, year = {2021}, pages = {5618}, abstract = {

Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin.

}, doi = {10.1038/s41467-021-25583-7}, author = {van Dongen, Jenny and Gordon, Scott D and McRae, Allan F and Odintsova, Veronika V and Mbarek, Hamdi and Breeze, Charles E and Sugden, Karen and Lundgren, Sara and Castillo-Fernandez, Juan E and Hannon, Eilis and Moffitt, Terrie E and Hagenbeek, Fiona A and van Beijsterveldt, Catharina E M and Jan Hottenga, Jouke and Tsai, Pei-Chien and BIOS Consortium and Genetics of DNA Methylation Consortium and Min, Josine L and Hemani, Gibran and Ehli, Erik A and Paul, Franziska and Stern, Claudio D and Heijmans, Bastiaan T and Slagboom, P Eline and Daxinger, Lucia and van der Maarel, Silv{\`e}re M and de Geus, Eco J C and Willemsen, Gonneke and Montgomery, Grant W and Reversade, Bruno and Ollikainen, Miina and Kaprio, Jaakko and Spector, Tim D and Bell, Jordana T and Mill, Jonathan and Caspi, Avshalom and Martin, Nicholas G and Boomsma, Dorret I} } @article {447, title = {Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour}, journal = {Nature Human Behaviour}, volume = {5}, year = {2021}, pages = {1717{\textendash}1730}, abstract = {

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercours

}, doi = {10.1038/s41562-021-01135-3}, author = {Mills, Melinda C and Tropf, Felix C and Brazel, David M and van Zuydam, Natalie and Vaez, Ahmad and eQTLGen Consortium and BIOS Consortium and Human Reproductive Behaviour Consortium and Pers, Tune H and Snieder, Harold and Perry, John R B and Ong, Ken K and den Hoed, Marcel and Barban, Nicola and Day, Felix R} } @article {435, title = {Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction}, journal = {Nature Genetics}, volume = {53}, year = {2021}, pages = {35{\textendash}44}, abstract = {

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57\% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success.

}, doi = {10.1038/s41588-020-00754-2}, author = {Demange, Perline A and Malanchini, Margherita and Mallard, Travis T and Biroli, Pietro and Cox, Simon R and Grotzinger, Andrew D and Tucker-Drob, Elliot M and Abdellaoui, Abdel and Arseneault, Louise and van Bergen, Elsje and Boomsma, Dorret I and Caspi, Avshalom and Corcoran, David L and Domingue, Benjamin W and Harris, Kathleen Mullan and Ip, Hill F and Mitchell, Colter and Moffitt, Terrie E and Poulton, Richie and Prinz, Joseph A and Sugden, Karen and Wertz, Jasmin and Williams, Benjamin S and de Zeeuw, Eveline L and Belsky, Daniel W and Harden, K Paige and Nivard, Michel G} } @article {436, title = {Large-scale association analyses identify host factors influencing human gut microbiome composition}, journal = {Nature Genetics}, volume = {53}, year = {2021}, pages = {156{\textendash}165}, abstract = {

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95\% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P \< 5 $\times$ 10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 $\times$ 10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 $\times$ 10-10 \< P \< 5 $\times$ 10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.

}, doi = {10.1038/s41588-020-00763-1}, author = {Kurilshikov, Alexander and Medina-Gomez, Carolina and Bacigalupe, Rodrigo and Radjabzadeh, Djawad and Wang, Jun and Demirkan, Ayse and Le Roy, Caroline I and Raygoza Garay, Juan Antonio and Finnicum, Casey T and Liu, Xingrong and Zhernakova, Daria V and Bonder, Marc Jan and Hansen, Tue H and Frost, Fabian and R{\"u}hlemann, Malte C and Turpin, Williams and Moon, Jee-Young and Kim, Han-Na and L{\"u}ll, Kreete and Barkan, Elad and Shah, Shiraz A and Fornage, Myriam and Szopinska-Tokov, Joanna and Wallen, Zachary D and Borisevich, Dmitrii and Agreus, Lars and Andreasson, Anna and Bang, Corinna and Bedrani, Larbi and Bell, Jordana T and Bisgaard, Hans and Boehnke, Michael and Boomsma, Dorret I and Burk, Robert D and Claringbould, Annique and Croitoru, Kenneth and Davies, Gareth E and van Duijn, Cornelia M and Duijts, Liesbeth and Falony, Gwen and Fu, Jingyuan and van der Graaf, Adriaan and Hansen, Torben and Homuth, Georg and Hughes, David A and Ijzerman, Richard G and Jackson, Matthew A and Jaddoe, Vincent W V and Joossens, Marie and J{\o}rgensen, Torben and Keszthelyi, Daniel and Knight, Rob and Laakso, Markku and Laudes, Matthias and Launer, Lenore J and Lieb, Wolfgang and Lusis, Aldons J and Masclee, Ad A M and Moll, Henriette A and Mujagic, Zlatan and Qibin, Qi and Rothschild, Daphna and Shin, Hocheol and S{\o}rensen, S{\o}ren J and Steves, Claire J and Thorsen, Jonathan and Timpson, Nicholas J and Tito, Raul Y and Vieira-Silva, Sara and V{\"o}lker, Uwe and V{\"o}lzke, Henry and V{\~o}sa, Urmo and Wade, Kaitlin H and Walter, Susanna and Watanabe, Kyoko and Weiss, Stefan and Weiss, Frank U and Weissbrod, Omer and Westra, Harm-Jan and Willemsen, Gonneke and Payami, Haydeh and Jonkers, Daisy M A E and Arias Vasquez, Alejandro and de Geus, Eco J C and Meyer, Katie A and Stokholm, Jakob and Segal, Eran and Org, Elin and Wijmenga, Cisca and Kim, Hyung-Lae and Kaplan, Robert C and Spector, Tim D and Uitterlinden, Andre G and Rivadeneira, Fernando and Franke, Andre and Lerch, Markus M and Franke, Lude and Sanna, Serena and D{\textquoteright}Amato, Mauro and Pedersen, Oluf and Paterson, Andrew D and Kraaij, Robert and Raes, Jeroen and Zhernakova, Alexandra} } @article {445, title = {Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity}, journal = {Brain and Behavior}, volume = {11}, year = {2021}, pages = {e02188}, abstract = {

BACKGROUND AND PURPOSE: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain.

METHODS: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations.

RESULTS: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters.

CONCLUSION: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.

}, keywords = {brain disorders, electroencephalography, ENIGMA, harmonization, imaging genetics, open science}, doi = {10.1002/brb3.2188}, author = {Smit, Dirk J A and Andreassen, Ole A and Boomsma, Dorret I and Burwell, Scott J and Chorlian, David B and de Geus, Eco J C and Elvs\aashagen, Torbj{\o}rn and Gordon, Reyna L and Harper, Jeremy and Hegerl, Ulrich and Hensch, Tilman and Iacono, William G and Jawinski, Philippe and J{\"o}nsson, Erik G and Luykx, Jurjen J and Magne, Cyrille L and Malone, Stephen M and Medland, Sarah E and Meyers, Jacquelyn L and Moberget, Torgeir and Porjesz, Bernice and Sander, Christian and Sisodiya, Sanjay M and Thompson, Paul M and van Beijsterveldt, Catharina E M and van Dellen, Edwin and Via, Marc and Wright, Margaret J} } @article {443, title = {Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability}, journal = {Nature Communications}, volume = {12}, year = {2021}, pages = {24}, abstract = {

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.

}, doi = {10.1038/s41467-020-19366-9}, author = {Lagou, Vasiliki and M{\"a}gi, Reedik and Hottenga, Jouke- Jan and Grallert, Harald and Perry, John R B and Bouatia-Naji, Nabila and Marullo, Letizia and Rybin, Denis and Jansen, Rick and Min, Josine L and Dimas, Antigone S and Ulrich, Anna and Zudina, Liudmila and G\aadin, Jesper R and Jiang, Longda and Faggian, Alessia and Bonnefond, Am{\'e}lie and Fadista, Joao and Stathopoulou, Maria G and Isaacs, Aaron and Willems, Sara M and Navarro, Pau and Tanaka, Toshiko and Jackson, Anne U and Montasser, May E and O{\textquoteright}Connell, Jeff R and Bielak, Lawrence F and Webster, Rebecca J and Saxena, Richa and Stafford, Jeanette M and Pourcain, Beate St and Timpson, Nicholas J and Salo, Perttu and Shin, So-Youn and Amin, Najaf and Smith, Albert V and Li, Guo and Verweij, Niek and Goel, Anuj and Ford, Ian and Johnson, Paul C D and Johnson, Toby and Kapur, Karen and Thorleifsson, Gudmar and Strawbridge, Rona J and Rasmussen-Torvik, Laura J and Esko, T{\~o}nu and Mihailov, Evelin and Fall, Tove and Fraser, Ross M and Mahajan, Anubha and Kanoni, Stavroula and Giedraitis, Vilmantas and Kleber, Marcus E and Silbernagel, G{\"u}nther and Meyer, Julia and M{\"u}ller-Nurasyid, Martina and Ganna, Andrea and Sarin, Antti-Pekka and Yengo, Loic and Shungin, Dmitry and Luan, Jian{\textquoteright}an and Horikoshi, Momoko and An, Ping and Sanna, Serena and Boettcher, Yvonne and Rayner, N William and Nolte, Ilja M and Zemunik, Tatijana and van Iperen, Erik and Kovacs, Peter and Hastie, Nicholas D and Wild, Sarah H and McLachlan, Stela and Campbell, Susan and Polasek, Ozren and Carlson, Olga and Egan, Josephine and Kiess, Wieland and Willemsen, Gonneke and Kuusisto, Johanna and Laakso, Markku and Dimitriou, Maria and Hicks, Andrew A and Rauramaa, Rainer and Bandinelli, Stefania and Thorand, Barbara and Liu, Yongmei and Miljkovic, Iva and Lind, Lars and Doney, Alex and Perola, Markus and Hingorani, Aroon and Kivimaki, Mika and Kumari, Meena and Bennett, Amanda J and Groves, Christopher J and Herder, Christian and Koistinen, Heikki A and Kinnunen, Leena and Faire, Ulf de and Bakker, Stephan J L and Uusitupa, Matti and Palmer, Colin N A and Jukema, J Wouter and Sattar, Naveed and Pouta, Anneli and Snieder, Harold and Boerwinkle, Eric and Pankow, James S and Magnusson, Patrik K and Krus, Ulrika and Scapoli, Chiara and de Geus, Eco J C N and Bl{\"u}her, Matthias and Wolffenbuttel, Bruce H R and Province, Michael A and Abecasis, Goncalo R and Meigs, James B and Hovingh, G Kees and Lindstr{\"o}m, Jaana and Wilson, James F and Wright, Alan F and Dedoussis, George V and Bornstein, Stefan R and Schwarz, Peter E H and T{\"o}njes, Anke and Winkelmann, Bernhard R and Boehm, Bernhard O and M{\"a}rz, Winfried and Metspalu, Andres and Price, Jackie F and Deloukas, Panos and K{\"o}rner, Antje and Lakka, Timo A and Keinanen-Kiukaanniemi, Sirkka M and Saaristo, Timo E and Bergman, Richard N and Tuomilehto, Jaakko and Wareham, Nicholas J and Langenberg, Claudia and M{\"a}nnist{\"o}, Satu and Franks, Paul W and Hayward, Caroline and Vitart, Veronique and Kaprio, Jaakko and Visvikis-Siest, Sophie and Balkau, Beverley and Altshuler, David and Rudan, Igor and Stumvoll, Michael and Campbell, Harry and van Duijn, Cornelia M and Gieger, Christian and Illig, Thomas and Ferrucci, Luigi and Pedersen, Nancy L and Pramstaller, Peter P and Boehnke, Michael and Frayling, Timothy M and Shuldiner, Alan R and Peyser, Patricia A and Kardia, Sharon L R and Palmer, Lyle J and Penninx, Brenda W and Meneton, Pierre and Harris, Tamara B and Navis, Gerjan and Harst, Pim van der and Smith, George Davey and Forouhi, Nita G and Loos, Ruth J F and Salomaa, Veikko and Soranzo, Nicole and Boomsma, Dorret I and Groop, Leif and Tuomi, Tiinamaija and Hofman, Albert and Munroe, Patricia B and Gudnason, Vilmundur and Siscovick, David S and Watkins, Hugh and Lecoeur, Cecile and Vollenweider, Peter and Franco-Cereceda, Anders and Eriksson, Per and Jarvelin, Marjo-Riitta and Stefansson, Kari and Hamsten, Anders and Nicholson, George and Karpe, Fredrik and Dermitzakis, Emmanouil T and Lindgren, Cecilia M and McCarthy, Mark I and Froguel, Philippe and Kaakinen, Marika A and Lyssenko, Valeriya and Watanabe, Richard M and Ingelsson, Erik and Florez, Jose C and Dupuis, Jos{\'e}e and Barroso, In{\^e}s and Morris, Andrew P and Prokopenko, Inga and Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC)} } @article {475, title = {The trans-ancestral genomic architecture of glycemic traits}, journal = {Nature Genetics}, year = {2021}, month = {05/2021}, pages = {840{\textendash}860}, abstract = {

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30\% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242\ loci (99 novel; P\ \<\ 5\ \×\ 10\−8), 80\% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99\% credible sets by a median of 37.5\%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

}, doi = {10.1038/s41588-021-00852-9}, author = {Chen, Ji and Spracklen, Cassandra N and Marenne, Ga{\"e}lle and Varshney, Arushi and Corbin, Laura J and Luan, Jian{\textquoteright}an and Willems, Sara M and Wu, Ying and Zhang, Xiaoshuai and Horikoshi, Momoko and Boutin, Thibaud S and M{\"a}gi, Reedik and Waage, Johannes and +100Authors} } @article {424, title = {Genetics and not shared environment explains familial resemblance in adult metabolomics data}, journal = {Human Genetics}, volume = {23}, year = {2020}, pages = {145{\textendash}155}, abstract = {

Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term \&$\#$39;metabolomics\&$\#$39; refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.

}, keywords = {classical twin design, enrichment analysis, heritability, metabolite classes, shared environment}, doi = {DOI: 10.1017/thg.2020.53}, author = {Pool, Ren{\'e} and Hagenbeek, Fiona A and Hendriks, Anne M and van Dongen, Jenny and Willemsen, Gonneke and de Geus, Eco and BBMRI Metabolomics Consortium and Willems van Dijk, Ko and Verhoeven, Aswin and Suchiman, H Eka and Beekman, Marian and Slagboom, P Eline and Harms, Amy C and Hankemeier, Thomas and Boomsma, Dorret I} } @article {427, title = {Heritability estimates for 361 blood metabolites across 40 genome-wide association studies}, journal = {Nature Communications}, volume = {11}, year = {2020}, pages = {39}, abstract = {

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50\% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify \>800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.

}, doi = {DOI: 10.1038/s41467-019-13770-6}, author = {Hagenbeek, Fiona A and Pool, Ren{\'e} and van Dongen, Jenny and Draisma, Harmen H M and Jan Hottenga, Jouke and Willemsen, Gonneke and Abdellaoui, Abdel and Fedko, Iryna O and den Braber, Anouk and Visser, Pieter Jelle and de Geus, Eco J C N and Willems van Dijk, Ko and Verhoeven, Aswin and Suchiman, H Eka and Beekman, Marian and Slagboom, P Eline and van Duijn, Cornelia M and BBMRI Metabolomics Consortium and Harms, Amy C and Hankemeier, Thomas and Bartels, Meike and Nivard, Michel G and Boomsma, Dorret I} } @article {423, title = {Identification, heritability, and relation with gene expression of novel DNA methylation loci for blood pressure}, journal = {Hypertension}, volume = {76}, year = {2020}, pages = {195{\textendash}205}, abstract = {

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with P\<1$\times$10-5. In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated (P\<1$\times$10-7) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with P\<0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61\% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84\% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100\% of the correlations of systolic BP with cg19693031 (TXNIP) and cg00716257 (JDP2) determined by environmental effects acting on both systolic BP and methylation levels.

}, keywords = {blood pressure, DNA methylation, epigenome, hypertension, twin study}, doi = {10.1161/HYPERTENSIONAHA.120.14973}, author = {Huang, Yisong and Ollikainen, Miina and Muniandy, Maheswary and Zhang, Tao and van Dongen, Jenny and Hao, Guang and van der Most, Peter J and Pan, Yue and Pervjakova, Natalia and Sun, Yan V and Hui, Qin and Lahti, Jari and Fraszczyk, Eliza and Lu, Xueling and Sun, Dianjianyi and Richard, Melissa A and Willemsen, Gonneke and Heikkil{\"a}, Kauko and Mateo Leach, Irene and Mononen, Nina and K{\"a}h{\"o}nen, Mika and Hurme, Mikko A and Raitakari, Olli T and Drake, Amanda J and Perola, Markus and Nuotio, Marja-Liisa and Huang, Yunfeng and Khulan, Batbayar and R{\"a}ikk{\"o}nen, Katri and Wolffenbuttel, Bruce H R and Zhernakova, Alexandra and Fu, Jingyuan and Zhu, Haidong and Dong, Yanbin and van Vliet-Ostaptchouk, Jana V and Franke, Lude and Eriksson, Johan G and Fornage, Myriam and Milani, Lili and Lehtim{\"a}ki, Terho and Vaccarino, Viola and Boomsma, Dorret I and van der Harst, Pim and de Geus, Eco J C and Salomaa, Veikko and Li, Shengxu and Chen, Wei and Su, Shaoyong and Wilson, James and Snieder, Harold and Kaprio, Jaakko and Wang, Xiaoling} } @article {441, title = {Measurement and genetic architecture of lifetime depression in the Netherlands as assessed by LIDAS (Lifetime Depression Assessment Self-report)}, journal = {Psychological Medicine}, volume = {51}, year = {2020}, pages = {1{\textendash}10}, abstract = {

BACKGROUND: Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34\%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression. METHODS: Within the Biobank Netherlands Internet Collaboration (BIONIC) project, we collected MDD data in eight cohorts involving 31 936 participants, using the online Lifetime Depression Assessment Self-report (LIDAS), and estimated the prevalence of current and lifetime MDD in 22 623 unrelated individuals. In a large Netherlands Twin Register (NTR) twin-family dataset (n $\approx$ 18 000), we estimated the heritability of MDD, and the prediction of MDD in a subset (n = 4782) through Polygenic Risk Score (PRS). RESULTS: Estimates of current and lifetime MDD prevalence were 6.7\% and 18.1\%, respectively, in line with population estimates based on validated psychiatric interviews. In the NTR heritability estimates were 0.34/0.30 (s.e. = 0.02/0.02) for current/lifetime MDD, respectively, showing that the LIDAS gives similar heritability rates for MDD as reported in the literature. The PRS predicted risk of MDD (OR 1.23, 95\% CI 1.15-1.3

}, keywords = {LIDAS, Lifetime Depression Assessment Self-report, major depressive disorder, online assessment tool, prevalence}, doi = {10.1017/S0033291720000100}, author = {Fedko, Iryna O and Hottenga, Jouke-Jan and Helmer, Quinta and Mbarek, Hamdi and Huider, Floris and Amin, Najaf and Beulens, Joline W and Bremmer, Marijke A and Elders, Petra J and Galesloot, Tessel E and Kiemeney, Lambertus A and van Loo, Hanna M and Picavet, H Susan J and Rutters, Femke and van der Spek, Ashley and van de Wiel, Anne M and van Duijn, Cornelia and de Geus, Eco J C and Feskens, Edith J M and Hartman, Catharina A and Oldehinkel, Albertine J and Smit, Jan H and Verschuren, W M Monique and Penninx, Brenda W J H and Boomsma, Dorret I and Bot, Mariska} } @article {290, title = {The Complex Role of Parental Separation in the Association between Family Conflict and Child Problem Behavior}, journal = {Journal of Clinical Child \& Adolescent Psychology}, year = {2019}, pages = {1-15}, abstract = {

Parental separation is a major adverse childhood experience. Parental separation is generally preceded by conflict, which is itself a risk factor for child problem behavior. Whether parental separation independent of conflict has negative effects on child problem behavior is unclear. This study was embedded in Generation R, a population-based cohort followed from fetal life until age 9\ years. Information on family conflict was obtained from 5,808 mothers and fathers. The 4-way decomposition method was used to apportion the effects of prenatal family conflict and parental separation on child problem behavior into 4 nonoverlapping components. Structural equation modeling was used to test bidirectional effects of child problem behavior and family conflict over time. Family conflict from pregnancy onward and parental separation each strongly predicted child problem behavior up to preadolescence according to maternal and paternal ratings. Using the 4-way decomposition method, we found evidence for a strong direct effect of prenatal family conflict on child problem behavior, for reference interaction, and for mediated interaction. The evidence for interaction implies that prenatal family conflict increased the children\’s vulnerability to the harmful effect of parental separation. There was no evidence of a pure indirect effect of parental separation on child problem behavior. Overall, results indicated that if parental separation occurs in families with low levels of conflict, parental separation does not predict more child problem behavior. Moreover, the bidirectional pattern suggested that child problem behavior influences the persistence of family conflict.

}, doi = {10.1080/15374416.2018.1520118}, url = {https://doi.org/10.1080/15374416.2018.1520118}, author = {Yllza Xerxa and Leslie A. Rescorla and Fadila Serdarevic and Marinus H. Van IJzendorn and Vincent W. Jaddoe and Frank C. Verhulst and Maartje P.C.M. Luijk and Henning Tiemeier} } @article {417, title = {DNA methylation signatures of breastfeeding in buccal cells collected in mid-childhood}, journal = {Nutrients}, volume = {11}, year = {2019}, pages = {2804}, abstract = {

Breastfeeding has long-term benefits for children that may be mediated via the epigenome. This pathway has been hypothesized, but the number of empirical studies in humans is small and mostly done by using peripheral blood as the DNA source. We performed an epigenome-wide association study (EWAS) in buccal cells collected around age nine (mean = 9.5) from 1006 twins recruited by the Netherlands Twin Register (NTR). An age-stratified analysis examined if effects attenuate with age (median split at 10 years; n10 = 489, mean age = 11.2). We performed replication analyses in two independent cohorts from the NTR (buccal cells) and the Avon Longitudinal Study of Parents and Children (ALSPAC) (peripheral blood), and we tested loci previously associated with breastfeeding in epigenetic studies. Genome-wide DNA methylation was assessed with the Illumina Infinium MethylationEPIC BeadChip (Illumina, San Diego, CA, USA) in the NTR and with the HumanMethylation450 Bead Chip in the ALSPAC. The duration of breastfeeding was dichotomized (\&$\#$39;never\&$\#$39; vs. \&$\#$39;ever\&$\#$39;). In the total sample, no robustly associated epigenome-wide significant CpGs were identified ($\alpha$ = 6.34 $\times$ 10-8). In the sub-group of children younger than 10 years, four significant CpGs were associated with breastfeeding after adjusting for child and maternal characteristics. In children older than 10 years, methylation differences at these CpGs were smaller and non-significant. The findings did not replicate in the NTR sample (n = 98; mean age = 7.5 years), and no nearby sites were associated with breastfeeding in the ALSPAC study (n = 938; mean age = 7.4). Of the CpG sites previously reported in the literature, three were associated with breastfeeding in children younger than 10 years, thus showing that these CpGs are associated with breastfeeding in buccal and blood cells. Our study is the first to show that breastfeeding is associated with epigenetic variation in buccal cells in children. Further studies are needed to investigate if methylation differences at these loci are caused by breastfeeding or by other unmeasured confounders, as well as what mechanism drives changes in associations with age.

}, keywords = {ALSPAC., breastfeeding, DNA methylation, EPIC, EWAS, NTR, twins}, doi = {10.3390/nu11112804}, author = {Odintsova, Veronika V and Hagenbeek, Fiona A and Suderman, Matthew and Caramaschi, Doretta and van Beijsterveldt, Catharina E M and Kallsen, Noah A and Ehli, Erik A and Davies, Gareth E and Sukhikh, Gennady T and Fanos, Vassilios and Relton, Caroline and Bartels, Meike and Boomsma, Dorret I and van Dongen, Jenny} } @article {411, title = {Epigenome-wide association study of attention-deficit/hyperactivity disorder symptoms in adults}, journal = {Biological Psychiatry}, volume = {86}, year = {2019}, pages = {599{\textendash}607}, abstract = {

BACKGROUND: Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts.

METHODS: An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Region-based analyses accounting for the correlation between nearby methylation sites were also performed.

RESULTS: One epigenome-wide significant differentially methylated position was detected in the Dunedin study, but meta-analysis did not detect differentially methylated positions that were robustly associated across cohorts. In region-based analyses, six significant differentially methylation regions (DMRs) were identified in the Netherlands Twin Register, 19 in the Dunedin study, and none in the Environmental Risk Longitudinal Twin Study. Of these DMRs, 92\% were associated with methylation quantitative trait loci, and 68\% showed moderate to large blood-brain correlations for DNA methylation levels. DMRs included six nonoverlapping DMRs (three in the Netherlands Twin Register, three in the Dunedin study) in the major histocompatibility complex, which were associated with expression of genes in the major histocompatibility complex, including C4A and C4B, previously implicated in schizophrenia.

CONCLUSIONS: Our findings point at new candidate loci involved in immune and neuronal functions that await further replication. Our work also illustrates the need for further research to examine to what extent epigenetic associations with psychiatric traits depend on characteristics such as age, comorbidities, exposures, and genetic background.

}, keywords = {ADHD, CAARS, DNA methylation, Epigenetic, EWAS, meta-analysis}, doi = {10.1016/j.biopsych.2019.02.016}, author = {van Dongen, Jenny and Zilh{\~a}o, Nuno R and Sugden, Karen and BIOS Consortium and Hannon, Eilis J and Mill, Jonathan and Caspi, Avshalom and Agnew-Blais, Jessica and Arseneault, Louise and Corcoran, David L and Moffitt, Terrie E and Poulton, Richie and Franke, Barbara and Boomsma, Dorret I} } @article {409, title = {Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight}, journal = {Nature Communications}, volume = {10}, year = {2019}, pages = {1893}, abstract = {

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from \−183 to 178 grams per 10\% increase in methylation (PBonferroni\ \<\ 1.06\ x\ 10\−7). In additional analyses in 7,278 participants, \<1.3\% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood.\ Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p\ = 6.12\ x\ 10\−74) and BMI in pregnancy (3/914, p = 1.13x10\−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

}, doi = {10.1038/s41467-019-09671-3}, author = {K{\"u}pers, Leanne K and Monnereau, Claire and Sharp, Gemma C and Yousefi, Paul and Salas, Lucas A and Ghantous, Akram and Page, Christian M and Reese, Sarah E and Wilcox, Allen J and Czamara, Darina and Starling, Anne P and Novoloaca, Alexei and Lent, Samantha and Roy, Ritu and Hoyo, Cathrine and Breton, Carrie V and Allard, Catherine and Just, Allan C and Bakulski, Kelly M and Holloway, John W and Everson, Todd M and Xu, Cheng-Jian and Huang, Rae-Chi and van der Plaat, Diana A and Wielscher, Matthias and Merid, Simon Kebede and Ullemar, Vilhelmina and Rezwan, Faisal I and Lahti, Jari and van Dongen, Jenny and Langie, Sabine A S and Richardson, Tom G and Magnus, Maria C and Nohr, Ellen A and Xu, Zongli and Duijts, Liesbeth and Zhao, Shanshan and Zhang, Weiming and Plusquin, Michelle and DeMeo, Dawn L and Solomon, Olivia and Heimovaara, Joosje H and Jima, Dereje D and Gao, Lu and Bustamante, Mariona and Perron, Patrice and Wright, Robert O and Hertz-Picciotto, Irva and Zhang, Hongmei and Karagas, Margaret R and Gehring, Ulrike and Marsit, Carmen J and Beilin, Lawrence J and Vonk, Judith M and Jarvelin, Marjo-Riitta and Bergstr{\"o}m, Anna and {\"O}rtqvist, Anne K and Ewart, Susan and Villa, Pia M and Moore, Sophie E and Willemsen, Gonneke and Standaert, Arnout R L and H\aaberg, Siri E and S{\o}rensen, Thorkild I A and Taylor, Jack A and R{\"a}ikk{\"o}nen, Katri and Yang, Ivana V and Kechris, Katerina and Nawrot, Tim S and Silver, Matt J and Gong, Yun Yun and Richiardi, Lorenzo and Kogevinas, Manolis and Litonjua, Augusto A and Eskenazi, Brenda and Huen, Karen and Mbarek, Hamdi and Maguire, Rachel L and Dwyer, Terence and Vrijheid, Martine and Bouchard, Luigi and Baccarelli, Andrea A and Croen, Lisa A and Karmaus, Wilfried and Anderson, Denise and de Vries, Maaike and Sebert, Sylvain and Kere, Juha and Karlsson, Robert and Arshad, Syed Hasan and H{\"a}m{\"a}l{\"a}inen, Esa and Routledge, Michael N and Boomsma, Dorret I and Feinberg, Andrew P and Newschaffer, Craig J and Govarts, Eva and Moisse, Matthieu and Fallin, M Daniele and Mel{\'e}n, Erik and Prentice, Andrew M and Kajantie, Eero and Almqvist, Catarina and Oken, Emily and Dabelea, Dana and Boezen, H Marike and Melton, Phillip E and Wright, Rosalind J and Koppelman, Gerard H and Trevisi, Letizia and Hivert, Marie-France and Sunyer, Jordi and Munthe-Kaas, Monica C and Murphy, Susan K and Corpeleijn, Eva and Wiemels, Joseph and Holland, Nina and Herceg, Zdenko and Binder, Elisabeth B and Davey Smith, George and Jaddoe, Vincent W V and Lie, Rolv T and Nystad, Wenche and London, Stephanie J and Lawlor, Debbie A and Relton, Caroline L and Snieder, Harold and Felix, Janine F} } @article {410, title = {Parenting and self-control across early to late adolescence: A three-level meta-analysis}, journal = {Perspectives on Psychological Science}, volume = {14}, year = {2019}, pages = {967{\textendash}1005}, abstract = {

Self-control plays a significant role in positive youth development. Although numerous self-control challenges occur during adolescence, some adolescents control themselves better than others. Parenting is considered a critical factor that distinguishes adolescents with good self-control from those with poor self-control, but existing findings are inconsistent. This meta-analysis summarizes the overall relationship between parenting and self-control among adolescents aged 10 to 22 years. The analysis includes 191 articles reporting 1,540 effect sizes (N = 164,459). The results show that parenting is associated with adolescents\&$\#$39; self-control both concurrently (r = .204, p \< .001) and longitudinally (r = .157, p \< .001). Longitudinal studies also reveal that adolescents\&$\#$39; self-control influences subsequent parenting (r = .155, p \< .001). Moderator analyses show that the effect sizes are largely invariant across cultures, ethnicities, age of adolescents, and parent and youth gender. Our results point to the importance of parenting in individual differences in adolescent self-control and vice versa.

}, keywords = {Adolescence, meta-analysis, parent-child relationship, parenting, self-control}, doi = {10.1177/1745691619863046}, author = {Li, Jian-Bin and Willems, Yayouk E and Stok, F Marijn and Dekovi{\'c}, Maja and Bartels, Meike and Finkenauer, Catrin} } @article {274, title = {Aggressive behaviour in childhood and adolescence: the role of smoking during pregnancy, evidence from four twin cohorts in the EU-ACTION consortium}, journal = {Psychological Medicine}, year = {2018}, pages = {1{\textendash}9}, abstract = {

BACKGROUND:

Maternal smoking during pregnancy (MSDP) has been linked to offspring\&$\#$39;s externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence.

METHODS:

Data came from four prospective twin cohorts - Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study - who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9-10; 12; 14-15 and 16-18.

RESULTS:

MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4\% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1\% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression.

CONCLUSIONS:

Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents\&$\#$39; aggressive behaviour.

}, doi = {10.1017/S0033291718001344}, author = {Malanchini, Margherita and Emily Smith-Woolley and Ayorech, Ziada and Kaili Rimfeld and Eva Krapohl and Vuoksimaa, Eero and Korhonen, Tellervo and Meike Bartels and van Beijsterveldt, Toos C.E.M. and Richard J. Rose and et al.} } @article {251, title = {The Associations between Callous-unemotional Traits and Symptoms of Conduct Problems, Hyperactivity and Emotional Problems: A Study of Adolescent Twins Screened for Neurodevelopmental Problems}, journal = {Journal of Abnormal Child Psychology}, year = {2018}, month = {May}, abstract = {

Callous-unemotional (CU) traits (e.g., lack of empathy, lack of guilt, shallow affect) are associated with severe and persistent conduct problems in youth. There is evidence showing a substantial genetic correlation between CU traits and conduct problems. The etiological associations between CU traits and other psychopathological symptoms, including symptoms of hyperactivity and emotional problems (such as anxiety and depression symptoms), have been less explored. To examine the etiological associations between CU traits and symptoms of conduct problems, hyperactivity and emotional problems separately through the use of a twin design. Participants were same-sex twin pairs (n{\th}inspace}={\th}inspace}426 twins; 42{\%} female; 43{\%} MZ; age{\th}inspace}={\th}inspace}15) drawn from the Child and Adolescents Twin Study in Sweden, a longitudinal study of twins born in Sweden. The sample was mainly composed of children who screenpositive on neurodevelopmental problems/mental health problems or at-risk children (i.e., screen-negative children considered to be genetically at-risk siblings). We used self-report measures of CU traits, conduct problems, hyperactivity and emotional problems. Model-fitting analyses were conducted using structural equation modeling. We found a strong positive genetic correlation between CU traits and conduct problems and a moderate genetic correlation between CU traits and hyperactivity. We also found a relatively modest, but significant negative genetic correlation between CU traits and emotional problems. Using a sample of adolescent twins screened for neurodevelopmental problems, we replicated previous findings that showed a strong genetic correlation between CU traits and conduct problems and we extended research by examining further the etiological associations between CU traits and symptoms of hyperactivity and emotional problems.

}, issn = {1573-2835}, doi = {10.1007/s10802-018-0439-1}, url = {https://doi.org/10.1007/s10802-018-0439-1}, author = {Saunders, Marie Claire and Anckars{\"a}ter, Henrik and Lundstr{\"o}m, Sebastian and Hellner, Clara and Lichtenstein, Paul and Fontaine, Nathalie M. G.} } @article {252, title = {Associations Between Conduct Disorder, Neurodevelopmental Problems and Psychopathic Personality Traits in a Swedish Twin Youth Population}, journal = {Journal of Psychopathology and Behavioral Assessment}, volume = {40}, year = {2018}, month = {Dec}, pages = {586{\textendash}592}, abstract = {

Previous research has found a complex relationship between psychopathic traits, neurodevelopmental problems (NDPs), and conduct disorder (CD) in children. This study explores associations between psychopathic traits, assessed with the Child Problematic Traits Inventory\–-Short Version (CPTI-SV), and CD in children with and without coexisting NDPs (i.e., attention deficit/hyperactivity disorder [ADHD] and autism spectrum disorder [ASD]) in a community-based sample of Swedish twins (n{\th}inspace}={\th}inspace}8762). Findings indicate weak to moderately strong correlations between psychopathic traits and CD, ADHD, and ASD, respectively. Furthermore, in univariable analyses, both psychopathic traits and NDPs displayed significant positive associations with being screened positive for CD, though only the grandiose-deceitful dimension of CPTI-SV and the ADHD domain concentration and attention deficits remained significantly associated with CD in a multivariable regression model. The results are relevant to screening and assessment in child and youth psychiatry, as a grandiose and deceitful interpersonal style may also be a valid sign of children at risk of developing CD.

}, issn = {1573-3505}, doi = {10.1007/s10862-018-9689-z}, url = {https://doi.org/10.1007/s10862-018-9689-z}, author = {Svensson, Olof and S{\"o}rman, Karolina and Durbeej, Natalie and Lichtenstein, Paul and Anckars{\"a}ter, Henrik and Kerekes, Nora and Nilsson, Thomas} } @article {249, title = {Characterizing the Relation Between Expression QTLs and Complex Traits: Exploring the Role of Tissue Specificity}, journal = {Behavior Genetics}, volume = {48}, year = {2018}, month = {Sep}, pages = {374{\textendash}385}, abstract = {

Measurement of gene expression levels and detection of eQTLs (expression quantitative trait loci) are difficult in tissues with limited sample availability, such as the brain. However, eQTL overlap between tissues might be high, which would allow for inference of eQTL functioning in the brain via eQTLs detected in readily accessible tissues, e.g. whole blood. Applying Stratified Linkage Disequilibrium Score Regression (SLDSR), we quantified the enrichment in polygenic signal of blood and brain eQTLs in genome-wide association studies (GWAS) of 11 complex traits. We looked at eQTLs discovered in 44 tissues by the Genotype-Tissue Expression (GTEx) consortium and two other large representative studies, and found no tissue-specific eQTL effects. Next, we integrated the GTEx eQTLs with regions associated with tissue-specific histone modifiers, and interrogated their effect on rheumatoid arthritis and schizophrenia. We observed substantially enriched effects of eQTLs located inside regions bearing modification H3K4me1 on schizophrenia, but not rheumatoid arthritis, and not tissue-specific. Finally, we extracted eQTLs associated with tissue-specific differentially expressed genes and determined their effects on rheumatoid arthritis and schizophrenia, these analysis revealed limited enrichment of eQTLs associated with gene specifically expressed in specific tissues. Our results pointed to strong enrichment of eQTLs in their effect on complex traits, without evidence for tissue-specific effects. Lack of tissue-specificity can be either due to a lack of statistical power or due to the true absence of tissue-specific effects. We conclude that eQTLs are strongly enriched in GWAS signal and that the enrichment is not specific to the eQTL discovery tissue. Until sample sizes for eQTL discovery grow sufficiently large, working with relatively accessible tissues as proxy for eQTL discovery is sensible and restricting lookups for GWAS hits to a specific tissue for which limited samples are available might not be advisable.

}, issn = {1573-3297}, doi = {10.1007/s10519-018-9914-2}, url = {https://doi.org/10.1007/s10519-018-9914-2}, author = {Ip, Hill F. and Jansen, Rick and Abdellaoui, Abdel and Meike Bartels and UK Brain Expression Consortium and Ryten, Mina and Hardy, John and Weale, Michael E. and Ramasamy, Adaikalavan and Forabosco, Paola and Matarin, Mar and Vandrovcova, Jana and Botia, Juan A. and D{\textquoteright}Sa, Karishma and Guelfi, Sebastian and Smith, Colin and Walker, Robert and Reynolds, Regina H. and Zhang, David and Trabzuni, Daniah and Dorret I. Boomsma and Michel G. Nivard} } @article {259, title = {Differences in exam performance between pupils attending selective and non-selective schools mirror the genetic differences between them}, volume = {3}, year = {2018}, month = {2018/03/23}, pages = {3}, abstract = {

On average, students attending selective schools outperform their non-selective counterparts in national exams. These differences are often attributed to value added by the school, as well as factors schools use to select pupils, including ability, achievement and, in cases where schools charge tuition fees or are located in affluent areas, socioeconomic status. However, the possible role of DNA differences between students of different schools types has not yet been considered. We used a UK-representative sample of 4814 genotyped students to investigate exam performance at age 16 and genetic differences between students in three school types: state-funded, non-selective schools (\‘non-selective\’), state-funded, selective schools (\‘grammar\’) and private schools, which are selective (\‘private\’). We created a genome-wide polygenic score (GPS) derived from a genome-wide association study of years of education (EduYears). We found substantial mean genetic differences between students of different school types: students in non-selective schools had lower EduYears GPS compared to those in grammar (d\ =\ 0.41) and private schools (d\ =\ 0.37). Three times as many students in the top EduYears GPS decile went to a selective school compared to the bottom decile. These results were mirrored in the exam differences between school types. However, once we controlled for factors involved in pupil selection, there were no significant genetic differences between school types, and the variance in exam scores at age 16 explained by school type dropped from 7\% to \<1\%. These results show that genetic and exam differences between school types are primarily due to the heritable characteristics involved in pupil admission.

}, isbn = {2056-7936}, url = {https://doi.org/10.1038/s41539-018-0019-8}, author = {Emily Smith-Woolley and Pingault, Jean-Baptiste and Saskia Selzam and Kaili Rimfeld and Eva Krapohl and Sophie von Stumm and Asbury, Kathryn and Philip S. Dale and Young, Toby and Allen, Rebecca and Yulia Kovas and Robert Plomin} } @article {261, title = {DNA methylation age is associated with an altered hemostatic profile in a multi-ethnic meta-analysis}, journal = {Blood}, year = {2018}, abstract = {

Elevated epigenetic age is associated with an altered hemostatic factor profile and lower clotting time (aPTT).DNA methylation age is associated with mRNA levels of fibrinogen in multiple tissues. Many hemostatic factors are associated with age and age-related diseases, however much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we used European and African-ancestry participants who were meta-analyzed separately and combined via a random effects meta-analysis. All other measures only included participants of European-ancestry. We found that 1-year higher extrinsic epigenetic age as compared to chronological age was associated with higher fibrinogen (0.004 g/L per year; 95\% CI: 0.001, 0.007; P = 0.01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL per year; 95\% CI: 0.07, 0.20; P = 6.6x10-5) concentrations as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the three fibrinogen subunit-encoding genes (FGA, FGG, and FGB), in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a pro-coagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

}, issn = {0006-4971}, doi = {10.1182/blood-2018-02-831347}, url = {http://www.bloodjournal.org/content/early/2018/07/24/blood-2018-02-831347}, author = {Ward-Caviness, Cavin K. and Huffman, Jennifer E. and Evertt, Karl and Germain, Marine and van Dongen, Jenny and Hill, W. David and Jhun, Min A. and Brody, Jennifer A. and Ghanbari, Mohsen and Du, Lei and Roetker, Nicholas S. and de Vries, Paul S. and Waldenberger, Melanie and Gieger, Christian and Wolf, Petra and Prokisch, Holger and Koenig, Wolfgang and O{\textquoteright}Donnell, Christopher J. and Levy, Daniel and Liu, Chunyu and Truong, Vinh and Wells, Philip S. and Tr{\'e}gou{\"e}t, David-Alexandre and Tang, Weihong and Morrison, Alanna C. and Boerwinkle, Eric and Wiggins, Kerri L. and McKnight, Barbara and Guo, Xiuqing and Psaty, Bruce M. and Sotoodenia, Nona and Dorret I. Boomsma and Gonneke Willemsen and Lannie Ligthart and Deary, Ian J. and Zhao, Wei and Ware, Erin B. and Kardia, Sharon L.R. and Joyce B.J. Van Meurs and Uitterlinden, Andre G. and Franco, Oscar H. and Eriksson, Per and Franco-Cereceda, Anders and Pankow, James S. and Johnson, Andrew D. and Gagnon, France and Morange, Pierre-Emmanuel and de Geus, Eco J.C. and Starr, John M. and Smith, Jennifer A. and Dehghan, Abbas and Bj{\"o}rck, Hanna M. and Smith, Nicholas L. and Peters, Annette} } @article {227, title = {DNA methylation signatures of educational attainment}, volume = {3}, year = {2018}, month = {2018/03/23}, pages = {7}, abstract = {

Educational attainment is a key behavioural measure in studies of cognitive and physical health, and socioeconomic status. We measured DNA methylation at 410,746 CpGs (N\ =\ 4152) and identified 58 CpGs associated with educational attainment at loci characterized by pleiotropic functions shared with neuronal, immune and developmental processes. Associations overlapped with those for smoking behaviour, but remained after accounting for smoking at many CpGs: Effect sizes were on average 28\% smaller and genome-wide significant at 11 CpGs after adjusting for smoking and were 62\% smaller in never smokers. We examined sources and biological implications of education-related methylation differences, demonstrating correlations with maternal prenatal folate, smoking and air pollution signatures, and associations with gene expression in cis, dynamic methylation in foetal brain, and correlations between blood and brain. Our findings show that the methylome of lower-educated people resembles that of smokers beyond effects of their own smoking behaviour and shows traces of various other exposures.

}, isbn = {2056-7936}, url = {https://doi.org/10.1038/s41539-018-0020-2}, author = {Jenny van Dongen and Bonder, Marc Jan and Dekkers, Koen F. and Michel G. Nivard and van Iterson, Maarten and Gonneke Willemsen and Beekman, Marian and van der Spek, Ashley and Joyce B.J. Van Meurs and Franke, Lude and Bastiaan T. Heijmans and van Duijn, Cornelia M. and Slagboom, P. Eline and Dorret I. Boomsma} } @article {271, title = {Evidence for gene-environment correlation in child feeding: Links between common genetic variation for BMI in children and parental feeding practices}, journal = {PLOS Genetics}, volume = {14}, year = {2018}, month = {11}, pages = {1-19}, abstract = {

The parental feeding practices (PFPs) of excessive restriction of food intake (\‘restriction\’) and pressure to increase food consumption (\‘pressure\’) have been argued to causally influence child weight in opposite directions (high restriction causing overweight; high pressure causing underweight). However child weight could also \‘elicit\’ PFPs. A novel approach is to investigate gene-environment correlation between child genetic influences on BMI and PFPs. Genome-wide polygenic scores (GPS) combining BMI-associated variants were created for 10,346 children (including 3,320 DZ twin pairs) from the Twins Early Development Study using results from an independent genome-wide association study meta-analysis. Parental \‘restriction\’ and \‘pressure\’ were assessed using the Child Feeding Questionnaire. Child BMI standard deviation scores (BMI-SDS) were calculated from children\’s height and weight at age 10. Linear regression and fixed family effect models were used to test between- (n = 4,445 individuals) and within-family (n = 2,164 DZ pairs) associations between the GPS and PFPs. In addition, we performed multivariate twin analyses (n = 4,375 twin pairs) to estimate the heritabilities of PFPs and the genetic correlations between BMI-SDS and PFPs. The GPS was correlated with BMI-SDS (β = 0.20, p = 2.41x10-38). Consistent with the gene-environment correlation hypothesis, child BMI GPS was positively associated with \‘restriction\’ (β = 0.05, p = 4.19x10-4), and negatively associated with \‘pressure\’ (β = -0.08, p = 2.70x10-7). These results remained consistent after controlling for parental BMI, and after controlling for overall family contributions (within-family analyses). Heritabilities for \‘restriction\’ (43\% [40\–47\%]) and \‘pressure\’ (54\% [50\–59\%]) were moderate-to-high. Twin-based genetic correlations were moderate and positive between BMI-SDS and \‘restriction\’ (rA = 0.28 [0.23\–0.32]), and substantial and negative between BMI-SDS and \‘pressure\’ (rA = -0.48 [-0.52 - -0.44]. Results suggest that the degree to which parents limit or encourage children\’s food intake is partly influenced by children\’s genetic predispositions to higher or lower BMI. These findings point to an evocative gene-environment correlation in which heritable characteristics in the child elicit parental feeding behaviour.

}, doi = {10.1371/journal.pgen.1007757}, url = {https://doi.org/10.1371/journal.pgen.1007757}, author = {Saskia Selzam and McAdams, Tom A. and Jonathan R I Coleman and Carnell, Susan and Paul F O{\textquoteright}Reilly and Robert Plomin and Llewellyn, Clare H.} } @article {281, title = {From positive psychology to psychopathology: the continuum of attention-deficit hyperactivity disorder}, journal = {Journal of Child Psychology and Psychiatry}, volume = {59}, year = {2018}, pages = {203-212}, abstract = {

BACKGROUND:

Integration of positive psychology into clinical research and treatment has been slow. This integration can be facilitated by the conceptualisation of mental disorders as the high, symptomatic extreme of continuous normal variation. This assumes that there is also a low, positive extreme, which is, however, unchartered territory. This study aims to examine how well current measures capture the low extreme of mental disorder continua, using attention-deficit hyperactivity disorder (ADHD) as an example.

METHODS:

The ability of three validated scales to capture ADHD as a continuous trait was examined using Item Response Theory in a sample of 9,882 adolescents from the UK population-representative Twins Early Development Study. These scales were: the Strengths and Weakness of ADHD Symptoms and Normal behaviour scale (SWAN), Strength and Difficulties Questionnaire (SDQ - hyperactivity subscale), and Conners\&$\#$39; Parent Rating Scale (Conners).

RESULTS:

Only the SWAN reliably differentiated interindividual differences between participants lying at any level of the continuous ADHD latent trait, including the extreme low, positive end (z-scores from -3 to +3). The SDQ showed low reliability across the ADHD latent trait. In contrast, the Conners performed best at differentiating individuals scoring at or above the mean to the high symptomatic range (z-scores from 0 to +3). The SWAN was the only measure to provide indicators of \&$\#$39;positive mental health\&$\#$39;, endorsed in the presence of particularly good attentive abilities.

CONCLUSIONS:

Scales such as the SWAN that reliably capture ADHD as a continuous trait, including the positive end, are important for not missing meaningful variation in population-based studies. Indicators of positive mental health may be helpful in clinical practice, as positive attributes have been shown to directly influence as well as buffer negative effects of psychiatric symptoms.

}, keywords = {Attention-deficit hyperactivity disorder, continuum, dimension, positive psychology, quantitative trait}, doi = {10.1111/jcpp.12786}, url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/jcpp.12786}, author = {Greven, Corina U. and Buitelaar, Jan K. and Salum, Giovanni A.} } @article {279, title = {The genetics of university success}, volume = {8}, year = {2018}, month = {2018/10/18}, pages = {14579}, abstract = {

University success, which includes enrolment in and achievement at university, as well as quality of the university, have all been linked to later earnings, health and wellbeing. However, little is known about the causes and correlates of differences in university-level outcomes. Capitalizing on both quantitative and molecular genetic data, we perform the first genetically sensitive investigation of university success with a UK-representative sample of 3,000 genotyped individuals and 3,000 twin pairs. Twin analyses indicate substantial additive genetic influence on university entrance exam achievement (57\%), university enrolment (51\%), university quality (57\%) and university achievement (46\%). We find that environmental effects tend to be non-shared, although the shared environment is substantial for university enrolment. Furthermore, using multivariate twin analysis, we show moderate to high genetic correlations between university success variables (0.27\–0.76). Analyses using DNA alone also support genetic influence on university success. Indeed, a genome-wide polygenic score, derived from a 2016 genome-wide association study of years of education, predicts up to 5\% of the variance in each university success variable. These findings suggest young adults select and modify their educational experiences in part based on their genetic propensities and highlight the potential for DNA-based predictions of real-world outcomes, which will continue to increase in predictive power.

}, isbn = {2045-2322}, url = {https://doi.org/10.1038/s41598-018-32621-w}, author = {Emily Smith-Woolley and Ayorech, Ziada and Philip S. Dale and Sophie von Stumm and Robert Plomin} } @article {404, title = {A genome-wide association study for extremely high intelligence}, journal = {Molecular Psychiatry}, volume = {23}, year = {2018}, pages = {1226{\textendash}1232}, abstract = {

We used a case\–control genome-wide association (GWA) design with cases consisting of 1238 individuals from the top 0.0003 (~170 mean IQ) of the population distribution of intelligence and 8172 unselected population-based controls. The single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02), which is the highest so far for a cognitive phenotype, and significant genome-wide genetic correlations of 0.78 were observed with educational attainment and 0.86 with population IQ. Three variants in locus ADAM12 achieved genome-wide significance, although they did not replicate with published GWA analyses of normal-range IQ or educational attainment. A genome-wide polygenic score constructed from the GWA results accounted for 1.6\% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes. The gene family plexins, members of which are mutated in several monogenic neurodevelopmental disorders, was significantly enriched for associations with high IQ. This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population.

}, doi = {https://doi.org/10.1038/mp.2017.121}, author = {Zabaneh, D and Krapohl, E and Gaspar, H A and Curtis, C and Lee, S H and Patel, H and Newhouse, S and Wu, H M and Simpson, M A and Putallaz, M and Lubinski, D and Plomin, R and Breen, G} } @article {275, title = {A polygenic p factor for major psychiatric disorders}, journal = {Translational psychiatry}, volume = {8}, year = {2018}, month = {2018/10/02}, pages = {205205 - 205}, abstract = {

It has recently been proposed that a single dimension, called the p factor, can capture a person\&$\#$39;s liability to mental disorder. Relevant to the p hypothesis, recent genetic research has found surprisingly high genetic correlations between pairs of psychiatric disorders. Here, for the first time, we compare genetic correlations from different methods and examine their support for a genetic p factor. We tested the hypothesis of a genetic p factor by applying principal component analysis to matrices of genetic correlations between major psychiatric disorders estimated by three methods-family study, genome-wide complex trait analysis, and linkage-disequilibrium score regression-and on a matrix of polygenic score correlations constructed for each individual in a UK-representative sample of 7 026 unrelated individuals. All disorders loaded positively on a first unrotated principal component, which accounted for 57, 43, 35, and 22\% of the variance respectively for the four methods. Our results showed that all four methods provided strong support for a genetic p factor that represents the pinnacle of the hierarchical genetic architecture of psychopathology.

}, isbn = {2158-3188}, url = {https://www.ncbi.nlm.nih.gov/pubmed/30279410}, author = {Saskia Selzam and Jonathan R I Coleman and Caspi, Avshalom and Moffitt, Terrie E and Robert Plomin} } @article {285, title = {Psychopathy in detained boys: The search for primary and secondary variants in a clinical setting.}, journal = {Personality Disorders: Theory, Research, and Treatment}, volume = {9}, year = {2018}, month = {2018}, pages = {408 - 419}, abstract = {

This study investigates whether primary and secondary variants of psychopathy can be identified in an applied, forensic setting based on self-reports of psychopathy and anxiety. Data were available for two samples of detained boys (Sample A: N = 847, Sample B: N = 749). Using three psychopathy dimensions and anxiety as clustering variables, latent profile analysis arrived at 4 latent classes (LCs) that were tentatively labeled as control (LC1), high anxiety (LC2), moderate psychopathy (LC3), and high psychopathy (LC4). Boys in LC4 engaged in higher levels of alcohol/drug use, conduct problems, reactive and proactive aggression than their counterparts in LC1 and in higher levels of conduct problems, alcohol/drug use, and proactive aggression than boys in LC3. Findings further indicated that the risk for future nonviolent arrests was the highest in LC4 as compared with LC2 and LC3, though no class differences in risk for future violent arrests emerged. Overall, these findings were well replicated in Sample B. Exploratory analyses included additional measures of negative affect (depressed feeling and anger\–irritability), maltreatment, and/or number of past arrests (as proxy of a 4th psychopathy dimension) as clustering variables and identified all but 1 (LC3) of the 4 aforementioned LCs. Notwithstanding that our findings challenge the expected relevance of differentiating primary and secondary variants of youth psychopathy, they do suggest that it is possible to identify detained boys with high levels of psychopathic traits who display features associated with adult psychopathy. Implications for theory, research, and practice are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

}, keywords = {*Anxiety, *Behavior Problems, *Legal Detention, *Psychopathy, *Subtypes (Disorders), Adolescent Psychopathology, Aggressive Behavior, Antisocial Behavior, Human Males, Profiles (Measurement)}, isbn = {1949-2723(Electronic),1949-2715(Print)}, author = {Olivier F. Colins and Fanti, Kostas A. and Salekin, Randall T. and Mulder, Eva and Andershed, Henrik} } @article {286, title = {Structural Brain Connectivity in Childhood Disruptive Behavior Problems: A Multidimensional Approach}, journal = {Biological PsychiatryBiological Psychiatry}, year = {2018}, month = {08/2018}, abstract = {

BACKGROUND:

Studies of white matter connectivity in children with disruptive behavior have yielded inconsistent results, possibly owing to the trait\&$\#$39;s heterogeneity, which comprises diverse symptoms like physical aggression, irritability, and delinquency. This study examined associations of global and specific white matter connectivity with childhood disruptive behavior problems, while accounting for their complex multidimensionality.

METHODS:

In a large cross-sectional population-based study of 10-year-old preadolescents (n\ = 2567), we assessed four previously described empirically derived dimensions of disruptive behavior problems using the Child Behavior Checklist: physical aggression, irritability, disobedient behavior, and delinquent behavior. Global and specific white matter microstructure was assessed by diffusion tensor imaging.

RESULTS:

Global fractional anisotropy and mean diffusivity were not associated with broad measures of disruptive behavior, e.g., Child Behavior Checklist externalizing problems scale. Global fractional anisotropy was negatively associated with delinquent behavior (β\ =\ -.123, pfalse discovery rate adjusted\ = .028) and global mean diffusivity was positively associated with delinquent behavior (β\ = .205, pfalse discovery rate adjusted \< 0.001), suggesting reduced white matter microstructure in preadolescents with higher levels of delinquent behavior. Lower white matter microstructure in the inferior longitudinal fasciculus, superior longitudinal fasciculus, cingulum, and uncinate underlie these associations. Global white matter microstructure was not associated with physical aggression, irritability, or disobedient behavior.

CONCLUSIONS:

Delinquent behavior, a severe manifestation of childhood disruptive behavior, was associated with lower white matter microstructure in tracts connecting frontal and temporal lobes. These brain regions are involved in decision making, reward processing, and emotion regulation. This study demonstrated that incorporating the multidimensional nature of childhood disruptive behavior traits shows promise in advancing the search for elucidating neurobiological correlates of disruptive behavior.

}, isbn = {0006-3223}, url = {https://doi.org/10.1016/j.biopsych.2018.07.005}, author = {Koen Bolhuis and Ryan L. Muetzel and Stringaris, Argyris and J.J. Hudziak and Vincent W.V. Jaddoe and Manon H.J. Hillegers and Tonya White and Steven A. Kushner and Henning Tiemeier} } @article {403, title = {Why do children read more? The influence of reading ability on voluntary reading practices}, journal = {Journal of Child Psychology and Psychiatry}, volume = {59}, year = {2018}, pages = {1205{\textendash}1214}, abstract = {

BACKGROUND: This study investigates the causal relationships between reading and print exposure and investigates whether the amount children read outside school determines how well they read, or vice versa. Previous findings from behavioural studies suggest that reading predicts print exposure. Here, we use twin-data and apply the behaviour-genetic approach of direction of causality modelling, suggested by Heath et al. (), to investigate the causal relationships between these two traits.

METHOD: Partial data were available for a large sample of twin children (N = 11,559) and 262 siblings, all enrolled in the Netherlands Twin Register. Children were assessed around 7.5 years of age. Mothers completed questionnaires reporting children\&$\#$39;s time spent on reading activities and reading ability. Additional information on reading ability was available through teacher ratings and performance on national reading tests. For siblings reading test, results were available.

RESULTS: The reading ability of the twins was comparable to that of the siblings and national norms, showing that twin findings can be generalized to the population. A measurement model was specified with two latent variables, Reading Ability and Print Exposure, which correlated .41. Heritability analyses showed that Reading Ability was highly heritable, while genetic and environmental influences were equally important for Print Exposure. We exploited the fact that the two constructs differ in genetic architecture and fitted direction of causality models. The results supported a causal relationship running from Reading Ability to Print Exposure.

CONCLUSIONS: How much and how well children read are moderately correlated. Individual differences in print exposure are less heritable than individual differences in reading ability. Importantly, the present results suggest that it is the children\&$\#$39;s reading ability that determines how much they choose to read, rather than vice versa.

}, keywords = {behaviour-genetics, causal modelling, Direction of causality models, print exposure, reading skills, twin studies}, doi = {10.1111/jcpp.12910}, author = {van Bergen, Elsje and Snowling, Margaret J and de Zeeuw, Eveline L and van Beijsterveldt, Catharina E M and Dolan, Conor V and Boomsma, Dorret I} } @article {267, title = {ADHD Medication and Substance-Related Problems}, journal = {American Journal of Psychiatry}, volume = {174}, year = {2017}, pages = {877-885}, abstract = {

Objective: substance use disorders are major contributors to excess mortality among individuals with attention deficit hyperactivity disorder (ADHD), yet associations between pharmacological ADHD treatment and substance-related problems remain unclear. This study investigated concurrent and long-term associations between ADHD medication treatment and substance-related events.

Method: the authors analyzed 2005\–2014 commercial health care claims from 2,993,887 (47.2\% female) adolescent and adult ADHD patients. Within-individual analyses compared the risk of substance-related events (i.e., emergency department visits related to substance use disorders) during months in which patients received prescribed stimulant medication or atomoxetine relative to the risk during months in which they did not.

Results: in adjusted within-individual comparisons, relative to periods in which patients did not receive ADHD medication, male patients had 35\% lower odds of concurrent substance-related events when receiving medication (odds ratio=0.65, 95\% CI=0.64\–0.67), and female patients had 31\% lower odds of concurrent substance-related events (odds ratio=0.69, 95\% CI=0.67\–0.71). Moreover, male patients had 19\% lower odds of substance-related events 2 years after medication periods (odds ratio=0.81, 95\% CI=0.78\–0.85), and female patients had 14\% lower odds of substance-related events 2 years after medication periods (odds ratio=0.86, 95\% CI= 0.82\–0.91). Sensitivity analyses supported most findings but were less consistent for long-term associations among women.

Conclusions: these results provide evidence that receiving ADHD medication is unlikely to be associated with greater risk of substance-related problems in adolescence or adulthood. Rather, medication was associated with lower concurrent risk of substance-related events and, at least among men, lower long-term risk of future substance-related events.

}, doi = {10.1176/appi.ajp.2017.16060686}, url = {https://doi.org/10.1176/appi.ajp.2017.16060686}, author = {Quinn, Patrick D. and Chang, Zheng and Hur, Kwan and Gibbons, Robert D. and Benjamin B Lahey and Rickert, Martin E. and Sj{\"o}lander, Arvid and Lichtenstein, Paul and Henrik Larsson and D{\textquoteright}Onofrio, Brian M.} } @article {197, title = {Fine mapping genetic associations between the HLA region and extremely high intelligence}, journal = {Scientific Reports}, volume = {7}, year = {2017}, month = {2017}, pages = {41182}, abstract = {

General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely powered design, we investigated whether fine-mapping of the HLA region could narrow the missing heritability gap. Our case-control design included 1,393 cases with extremely high intelligence scores (top 0.0003 of the population equivalent to IQ\ \>\ 147) and 3,253 unselected population controls. We imputed variants in 200 genes across the HLA region, one SNP (rs444921) reached our criterion for study-wide significance. SNP-based heritability of the HLA variants was small and not significant (h(2)\ =\ 0.3\%, SE\ =\ 0.2\%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence.

}, isbn = {2045-2322}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259706/}, author = {Zabaneh, Delilah and Eva Krapohl and Simpson, Michael A and Miller, Mike B and Iacono, William G and McGue, Matt and Putallaz, Martha and Lubinski, David and Robert Plomin and Breen, Gerome} } @article {200, title = {Genome-Wide Polygenic Scores Predict Reading Performance Throughout the School Years}, journal = {Scientific Studies of Reading}, volume = {21}, year = {2017}, month = {2017/07/04}, pages = {334 - 349}, abstract = {

It is now possible to create individual-specific genetic scores, called genome-wide polygenic scores (GPS). We used a GPS for years of education (EduYears) to predict reading performance assessed at UK National Curriculum Key Stages 1 (age 7), 2 (age 12) and 3 (age 14) and on reading tests administered at ages 7 and 12 in a UK sample of 5,825 unrelated individuals. EduYears GPS accounts for up to 5\% of the variance in reading performance at age 14. GPS predictions remained significant after accounting for general cognitive ability and family socioeconomic status. Reading performance of children in the lowest and highest 12.5\% of the EduYears GPS distribution differed by a mean growth in reading ability of approximately two school years. It seems certain that polygenic scores will be used to predict strengths and weaknesses in education.

}, isbn = {1088-84381532-799X}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490720/}, author = {Saskia Selzam and Philip S. Dale and Wagner, Richard K and John C DeFries and Cederl{\"o}f, Martin and Paul F O{\textquoteright}Reilly and Eva Krapohl and Robert Plomin} } @article {199, title = {Predicting educational achievement from DNA}, journal = {Mol Psychiatry}, volume = {22}, year = {2017}, month = {2017/02//print}, pages = {267 - 272}, abstract = {

A genome-wide polygenic score (GPS), derived from a 2013 genome-wide association study (N=127,000), explained 2\% of the variance in total years of education (EduYears). In a follow-up study (N=329,000), a new EduYears GPS explains up to 4\%. Here, we tested the association between this latest EduYears GPS and educational achievement scores at ages 7, 12 and 16 in an independent sample of 5825 UK individuals. We found that EduYears GPS explained greater amounts of variance in educational achievement over time, up to 9\% at age 16, accounting for 15\% of the heritable variance. This is the strongest GPS prediction to date for quantitative behavioral traits. Individuals in the highest and lowest GPS septiles differed by a whole school grade at age 16. Furthermore, EduYears GPS was associated with general cognitive ability (~3.5\%) and family socioeconomic status (~7\%). There was no evidence of an interaction between EduYears GPS and family socioeconomic status on educational achievement or on general cognitive ability. These results are a harbinger of future widespread use of GPS to predict genetic risk and resilience in the social and behavioral sciences.

}, isbn = {1359-4184}, url = {http://dx.doi.org/10.1038/mp.2016.107}, author = {Saskia Selzam and Eva Krapohl and Sophie von Stumm and Paul F O{\textquoteright}Reilly and Kaili Rimfeld and Yulia Kovas and Philip S. Dale and Lee,J J and Robert Plomin} } @article {256, title = {Predictive validity of parent- and self-rated ADHD symptoms in adolescence on adverse socioeconomic and health outcomes}, journal = {European Child {\&} Adolescent Psychiatry}, volume = {26}, year = {2017}, month = {Jul}, pages = {857{\textendash}867}, abstract = {

There is scarcity of research investigating the validity of self-report of attention deficit hyperactivity disorder (ADHD) symptoms compared to other informants, such as parents. This study aimed to compare the predictive associations of ADHD symptoms rated by parents and their children across adolescence on a range of adverse socioeconomic and health outcomes in early adulthood. Parent- and self-rated ADHD symptoms were assessed in 2960 individuals in early (13\–14\ years) and late adolescence (16\–17\ years). Logistic regression analyses were used to compare the associations between parent- and self-rated ADHD symptoms at both time points and adverse life outcomes in young adulthood obtained from Swedish national registries. Both parent- and self-ratings of ADHD symptoms were associated with increased risk for adverse outcomes, although associations of parent-ratings were more often statistically significant and were generally stronger (OR\ =\ 1.12\–1.49, p\ \<\ 0.05) than self-ratings (OR\ =\ 1.07\–1.17, p\ \<\ 0.05). After controlling for the other informant, parent-ratings of ADHD symptoms in both early and late adolescence significantly predicted academic and occupational failure, criminal convictions and traffic-related injuries, while self-ratings of ADHD symptoms only in late adolescence predicted substance use disorder and academic failure. Our findings suggest that both parent- and self-ratings of ADHD symptoms in adolescence provides valuable information on risk of future adverse socioeconomic and health outcomes, however, self-ratings are not valuable once parent-ratings have been taken into account in predicting most outcomes. Thus, clinicians and researchers should prioritize parent-ratings over self-ratings.

}, issn = {1435-165X}, doi = {10.1007/s00787-017-0957-3}, url = {https://doi.org/10.1007/s00787-017-0957-3}, author = {Du Rietz, Ebba and Kuja-Halkola, Ralf and Brikell, Isabell and Jangmo, Andreas and Sariaslan, Amir and Lichtenstein, Paul and Kuntsi, Jonna and Henrik Larsson} } @article {198, title = {Weak associations between pubertal development and psychiatric and behavioral problems}, journal = {Translational Psychiatry}, volume = {7}, year = {2017}, month = {2017/04/}, pages = {e1098 - }, abstract = {

Pubertal development has been associated with adverse outcomes throughout adolescence and adulthood. However, much of the previous literature has categorized outcome variables and pubertal timing measures for ease of mean difference or odds ratio interpretation. We use a UK-representative sample of over 5000 individuals drawn from the Twins Early Development Study to extend this literature by adopting an individual differences approach and emphasizing effect sizes. We investigate a variety of psychiatric and behavioral measures collected longitudinally at ages 11, 14 and 16, for multiple raters and for males and females separately. In addition, we use two measures of pubertal development: the Pubertal Development Scale at each age, as well as the age of menarche for girls. We found that pubertal development, however assessed, was linearly associated with a range of psychiatric and behavioral outcomes; however, the effect sizes of these associations were modest for both males and females with most correlations between \−0.10 and 0.10. Our systematic analysis of associations between pubertal development, and psychiatric and behavioral problems is the most comprehensive to date. The results showing linearity of the effects of pubertal development support an individual differences approach, treating both pubertal development and associated outcomes as continuous rather than categorical variables. We conclude that pubertal development explains little variance in psychiatric and behavioral outcomes (\<1\% on average). The small effect sizes indicate that the associations are weak and should not warrant major concern at least in non-clinical populations.

}, isbn = {2158-3188}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416703/}, author = {Emily Smith-Woolley and Kaili Rimfeld and Robert Plomin} } @article {250, title = {Association between prescription of major psychotropic medications and violent reoffending after prison release}, journal = {JAMA}, volume = {316}, year = {2016}, pages = {1798-1807}, doi = {10.1001/jama.2016.15380}, url = {+ http://dx.doi.org/10.1001/jama.2016.15380}, author = {Chang Z and Lichtenstein P and L{\r a}ngstr{\"o}m N and Larsson H and Fazel S} } @article {128, title = {Genetic and environmental influences interact with age and sex in shaping the human methylome}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016/04/07}, abstract = {

The methylome is subject to genetic and environmental effects. Their impact may depend on sex and age, resulting in sex- and age-related physiological variation and disease susceptibility. Here we estimate the total heritability of DNA methylation levels in whole blood and estimate the variance explained by common single nucleotide polymorphisms at 411,169 sites in 2,603 individuals from twin families, to establish a catalogue of between-individual variation in DNA methylation. Heritability estimates vary across the genome (mean=19\%) and interaction analyses reveal thousands of sites with sex-specific heritability as well as sites where the environmental variance increases with age. Integration with previously published data illustrates the impact of genome and environment across the lifespan at methylation sites associated with metabolic traits, smoking and ageing. These findings demonstrate that our catalogue holds valuable information on locations in the genome where methylation variation between people may reflect disease-relevant environmental exposures or genetic variation.

}, url = {http://dx.doi.org/10.1038/ncomms11115}, author = {Jenny van Dongen and Michel G. Nivard and Gonneke Willemsen and Hottenga, Jouke-Jan and Helmer, Quinta and Conor V Dolan and Ehli, Erik A. and Gareth E Davies and van Iterson, Maarten and Breeze, Charles E. and Beck, Stephan and BIOS Consortium and Suchiman, H. Eka and Jansen, Rick and Joyce B.J. Van Meurs and Bastiaan T. Heijmans and Slagboom, P. Eline and Dorret I. Boomsma} } @article {102, title = {Longitudinal heritability of childhood aggression.}, journal = {Am J Med Genet B Neuropsychiatr Genet}, year = {2016}, month = {2016 Jan 19}, abstract = {

The genetic and environmental contributions to the variation and longitudinal stability in childhood aggressive behavior were assessed in two large twin cohorts, the Netherlands Twin Register (NTR), and the Twins Early Development Study (TEDS; United Kingdom). In NTR, maternal ratings on aggression from the Child Behavior Checklist (CBCL) were available for 10,765 twin pairs at age 7, for 8,557 twin pairs at age 9/10, and for 7,176 twin pairs at age 12. In TEDS, parental ratings of conduct disorder from the Strength and Difficulty Questionnaire (SDQ) were available for 6,897 twin pairs at age 7, for 3,028 twin pairs at age 9 and for 5,716 twin pairs at age 12. In both studies, stability and heritability of aggressive behavioral problems was high. Heritability was on average somewhat, but significantly, lower in TEDS (around 60\%) than in NTR (between 50\% and 80\%) and sex differences were slightly larger in the NTR sample. In both studies, the influence of shared environment was similar: in boys shared environment explained around 20\% of the variation in aggression across all ages while in girls its influence was absent around age 7 and only came into play at later ages. Longitudinal genetic correlations were the main reason for stability of aggressive behavior. Individual differences in CBCL-Aggressive Behavior and SDQ-Conduct disorder throughout childhood are driven by a comparable but significantly different genetic architecture. \© 2016 Wiley Periodicals, Inc.

}, issn = {1552-485X}, doi = {10.1002/ajmg.b.32420}, author = {Porsch, Robert M and Christel Middeldorp and Cherny, Stacey S and Eva Krapohl and Catharina E. M. van Beijsterveldt and Loukola, Anu and Korhonen, Tellervo and Pulkkinen, Lea and Corley, Robin and Rhee, Soo and Kaprio, Jaakko and Rose, Richard R and Hewitt, John K and Sham, Pak and Robert Plomin and Dorret I. Boomsma and Meike Bartels} } @article {196, title = {Publication Trends Over 55 Years of Behavioral Genetic Research}, journal = {Behavior Genetics}, volume = {46}, year = {2016}, month = {Sep}, pages = {603{\textendash}607}, abstract = {

We document the growth in published papers on behavioral genetics for 5-year intervals from 1960 through 2014. We used 1861 papers published in Behavior Genetics to train our search strategy which, when applied to Ovid PsychINFO, selected more than 45,000 publications. Five trends stand out: (1) the number of behavioral genetic publications has grown enormously; nearly 20,000 papers were published in 2010\–2014. (2) The number of human quantitative genetic (QG) publications (e.g., twin and adoption studies) has steadily increased with more than 3000 papers published in 2010\–2014. (3) The number of human molecular genetic (MG) publications increased substantially from about 2000 in 2000\–2004 to 5000 in 2005\–2009 to 9000 in 2010\–2014. (4) Nonhuman publications yielded similar trends. (5) Although there has been exponential growth in MG publications, both human and nonhuman QG publications continue to grow. A searchable resource of this corpus of behavioral genetic papers is freely available online at http://www.teds.ac.uk/public{\_}datasets.html and will be updated annually.

}, issn = {1573-3297}, doi = {10.1007/s10519-016-9786-2}, url = {https://doi.org/10.1007/s10519-016-9786-2}, author = {Ayorech, Ziada and Saskia Selzam and Emily Smith-Woolley and Knopik, Valerie S. and Neiderhiser, Jenae M. and John C DeFries and Robert Plomin} } @article {195, title = {Rotation is visualisation, 3D is 2D: using a novel measure to investigate the genetics of spatial ability}, journal = {Scientific Reports}, volume = {6}, year = {2016}, month = {2016}, pages = {30545}, abstract = {

Spatial abilities\–defined broadly as the capacity to manipulate mental representations of objects and the relations between them\–have been studied widely, but with little agreement reached concerning their nature or structure. Two major putative spatial abilities are \“mental rotation\” (rotating mental models) and \“visualisation\” (complex manipulations, such as identifying objects from incomplete information), but inconsistent findings have been presented regarding their relationship to one another. Similarly inconsistent findings have been reported for the relationship between two- and three-dimensional stimuli. Behavioural genetic methods offer a largely untapped means to investigate such relationships. 1,265 twin pairs from the Twins Early Development Study completed the novel \“Bricks\” test battery, designed to tap these abilities in isolation. The results suggest substantial genetic influence unique to spatial ability as a whole, but indicate that dissociations between the more specific constructs (rotation and visualisation, in 2D and 3D) disappear when tested under identical conditions: they are highly correlated phenotypically, perfectly correlated genetically (indicating that the same genetic influences underpin performance), and are related similarly to other abilities. This has important implications for the structure of spatial ability, suggesting that the proliferation of apparent sub-domains may sometimes reflect idiosyncratic tasks rather than meaningful dissociations.

}, isbn = {2045-2322}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967849/}, author = {Shakeshaft, Nicholas G and Kaili Rimfeld and Schofield, Kerry L and Saskia Selzam and Malanchini, Margherita and Rodic, Maja and Yulia Kovas and Robert Plomin} } @article {101, title = {A genome-wide approach to children{\textquoteright}s aggressive behavior: The EAGLE consortium.}, journal = {Am J Med Genet B Neuropsychiatr Genet}, year = {2015}, month = {2015 Jun 18}, abstract = {

Individual differences in aggressive behavior emerge in early childhood and predict persisting behavioral problems and disorders. Studies of antisocial and severe aggression in adulthood indicate substantial underlying biology. However, little attention has been given to genome-wide approaches of aggressive behavior in children. We analyzed data from nine population-based studies and assessed aggressive behavior using well-validated parent-reported questionnaires. This is the largest sample exploring children\&$\#$39;s aggressive behavior to date (N\ =\ 18,988), with measures in two developmental stages (N\ =\ 15,668 early childhood and N\ =\ 16,311 middle childhood/early adolescence). First, we estimated the additive genetic variance of children\&$\#$39;s aggressive behavior based on genome-wide SNP information, using genome-wide complex trait analysis (GCTA). Second, genetic associations within each study were assessed using a quasi-Poisson regression approach, capturing the highly right-skewed distribution of aggressive behavior. Third, we performed meta-analyses of genome-wide associations for both the total age-mixed sample and the two developmental stages. Finally, we performed a gene-based test using the summary statistics of the total sample. GCTA quantified variance tagged by common SNPs (10-54\%). The meta-analysis of the total sample identified one region in chromosome 2 (2p12) at near genome-wide significance (top SNP rs11126630, P\ =\ 5.30\ \×\ 10(-8) ). The separate meta-analyses of the two developmental stages revealed suggestive evidence of association at the same locus. The gene-based analysis indicated association of variation within AVPR1A with aggressive behavior. We conclude that common variants at 2p12 show suggestive evidence for association with childhood aggression. Replication of these initial findings is needed, and further studies should clarify its biological meaning. \© 2015 Wiley Periodicals, Inc.

}, issn = {1552-485X}, doi = {10.1002/ajmg.b.32333}, author = {Pappa, Irene and St Pourcain, Beate and Benke, Kelly and Cavadino, Alana and Hakulinen, Christian and Michel G. Nivard and Nolte, Ilja M and Tiesler, Carla M T and Marian J Bakermans-Kranenburg and Gareth E Davies and David M Evans and Geoffroy, Marie-Claude and Grallert, Harald and Groen-Blokhuis, Maria M and J.J. Hudziak and Kemp, John P and Keltikangas-J{\"a}rvinen, Liisa and McMahon, George and Mileva-Seitz, Viara R and Motazedi, Ehsan and Power, Christine and Raitakari, Olli T and Ring, Susan M and Rivadeneira, Fernando and Rodriguez, Alina and Scheet, Paul A and Sepp{\"a}l{\"a}, Ilkka and Snieder, Harold and Standl, Marie and Thiering, Elisabeth and Timpson, Nicholas J and Veenstra, Ren{\'e} and Velders, Fleur P and Whitehouse, Andrew J O and Smith, George Davey and Heinrich, Joachim and Hypponen, Elina and Lehtim{\"a}ki, Terho and Christel Middeldorp and Oldehinkel, Albertine J and Pennell, Craig E and Dorret I. Boomsma and Henning Tiemeier} } @article {100, title = {Out of Control Identifying the Role of Self-Control Strength in Family Violence}, journal = {Current Directions in Psychological Science}, volume = {24}, year = {2015}, pages = {261{\textendash}266}, abstract = {

Family violence is common and brings tremendous costs to individuals, relationships, and society. Victims are vulnerable to negative outcomes across a host of dimensions, including cognitive performance, impulse control, emotion regulation, and physical health. Links between family violence and various problems have been established, yet the specific processes underlying these associations are poorly understood, resulting in the stunted development of effective interventions. This article addresses two key questions: How and why does family violence cause these myriad problems? The self-control strength model of family violence provides novel answers. The model integrates components of existing theories, extending them by pinpointing self-control strength as an explanatory and predictive factor, and can serve as a framework for interventions.

}, doi = {10.1177/0963721415570730}, url = {http://cdp.sagepub.com/content/24/4/261.abstract}, author = {Catrin Finkenauer and Buyukcan-Tetik, Asuman and Baumeister, Roy F and Schoemaker, Kim and Meike Bartels and Vohs, Kathleen D} }