@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 {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} }