@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 {433, title = {Genetic meta-analysis of twin birth weight shows high genetic correlation with singleton birth weight}, journal = {Human Molecular Genetics}, volume = {30}, year = {2021}, pages = {1894{\textendash}1905}, abstract = {

Birth weight (BW) is an important predictor of newborn survival and health and has associations with many adult health outcomes, including cardiometabolic disorders, autoimmune diseases and mental health. On average, twins have a lower BW than singletons as a result of a different pattern of fetal growth and shorter gestational duration. Therefore, investigations into the genetics of BW often exclude data from twins, leading to a reduction in sample size and remaining ambiguities concerning the genetic contribution to BW in twins. In this study, we carried out a genome-wide association meta-analysis of BW in 42 212 twin individuals and found a positive correlation of beta values (Pearson\&$\#$39;s r = 0.66, 95\% confidence interval [CI]: 0.47-0.77) with 150 previously reported genome-wide significant variants for singleton BW. We identified strong positive genetic correlations between BW in twins and numerous anthropometric traits, most notably with BW in singletons (genetic correlation [rg] = 0.92, 95\% CI: 0.66-1.18). Genetic correlations of BW in twins with a series of health-related traits closely resembled those previously observed for BW in singletons. Polygenic scores constructed from a genome-wide association study on BW in the UK Biobank demonstrated strong predictive power in a target sample of Dutch twins and singletons. Together, our results indicate that a similar genetic architecture underlies BW in twins and singletons and that future genome-wide studies might benefit from including data from large twin registers.

}, doi = {10.1093/hmg/ddab121}, author = {Beck, Jeffrey J and Pool, Ren{\'e} and van de Weijer, Margot and Chen, Xu and Krapohl, Eva and Gordon, Scott D and Nygaard, Marianne and Debrabant, Birgit and Palviainen, Teemu and van der Zee, Matthijs D and Baselmans, Bart and Finnicum, Casey T and Yi, Lu and Lundstr{\"o}m, Sebastian and van Beijsterveldt, Toos and Christiansen, Lene and Heikkil{\"a}, Kauko and Kittelsrud, Julie and Loukola, Anu and Ollikainen, Miina and Christensen, Kaare and Martin, Nicholas G and Plomin, Robert and Nivard, Michel and Bartels, Meike and Dolan, Conor and Willemsen, Gonneke and de Geus, Eco and Almqvist, Catarina and Magnusson, Patrik K E and Mbarek, Hamdi and Ehli, Erik A and Boomsma, Dorret I and Hottenga, Jouke-Jan} } @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 {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} }