@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 {283, title = {Unraveling the Genetic and Environmental Relationship Between Well-Being and Depressive Symptoms Throughout the Lifespan}, journal = {Frontiers in Psychiatry}, volume = {9}, year = {2018}, pages = {261}, abstract = {

Whether well-being and depressive symptoms can be considered as two sides of the same coin is widely debated. The aim of this study was to gain insight into the etiology of the association between well-being and depressive symptoms across the lifespan. In a large twin-design, including data from 43,427 twins between age 7 and 99, we estimated the association between well-being and depressive symptoms throughout the lifespan and assessed genetic and environmental contributions to the observed overlap. For both well-being (range 31\% \–47\%) and depressive symptoms (range 50\%-61\%), genetic factors explained a substantial part of the phenotypic variance across the lifespan. Phenotypic correlations between well-being and depressive symptoms across ages ranged from -.34 in childhood to -.49 in adulthood. In children, genetic effects explained 49\% of the phenotypic correlation while in adolescents and young adults, genetic effects explained 60\% to 77\% of the phenotypic correlations. Moderate to high genetic correlations (ranging from -0.60 to -0.66) were observed in adolescence and adulthood, while in childhood environmental correlations were substantial but genetic correlations small. Our results suggest that in childhood genetic and environmental effects are about equally important in explaining the relationship between well-being and depressive symptoms. From adolescence onwards, the role of genetic effects increases compared to environmental effects. These results provided more insights into the etiological underpinnings of well-being and depressive symptoms, possibly allowing to articulate better strategies for health promotion and resource allocation in the future.

}, issn = {1664-0640}, doi = {10.3389/fpsyt.2018.00261}, url = {https://www.frontiersin.org/article/10.3389/fpsyt.2018.00261}, author = {Bart M. L. Baselmans and Willems, Yayouk E. and Catharina E. M. van Beijsterveldt and Lannie Ligthart and Gonneke Willemsen and Conor V Dolan and Dorret I. Boomsma and Meike Bartels} } @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 {264, title = {Joint developmental trajectories of internalizing and externalizing disorders between childhood and adolescence}, journal = {Development and Psychopathology}, volume = {-1}, year = {2016}, month = {07}, pages = {1-10}, abstract = {

This study sought to identify trajectories of DSM-IV based internalizing (INT) and externalizing (EXT) problem scores across childhood and adolescence and to provide insight into the comorbidity by modeling the co-occurrence of INT and EXT trajectories. INT and EXT were measured repeatedly between age 7 and age 15 years in over 7,000 children and analyzed using growth mixture models. Five trajectories were identified for both INT and EXT, including very low, low, decreasing, and increasing trajectories. In addition, an adolescent onset trajectory was identified for INT and a stable high trajectory was identified for EXT. Multinomial regression showed that similar EXT and INT trajectories were associated. However, the adolescent onset INT trajectory was independent of high EXT trajectories, and persisting EXT was mainly associated with decreasing INT. Sex and early life environmental risk factors predicted EXT and, to a lesser extent, INT trajectories. The association between trajectories indicates the need to consider comorbidity when a child presents with INT or EXT disorders, particularly when symptoms start early. This is less necessary when INT symptoms start at adolescence. Future studies should investigate the etiology of co-occurring INT and EXT and the specific treatment needs of these severely affected children.

}, doi = {10.1017/S0954579416000572}, author = {Michel G. Nivard and Gitta Lubke and Conor V Dolan and David M Evans and St. Pourcain, B and R. Munaf{\`o}, Marcus and Christel Middeldorp} } @article {95, title = {Methylation as an epigenetic source of random genetic effects in the classical twin design}, journal = {Advances in Genomics and Genetics, Dove Medical Press}, volume = {5}, year = {2015}, month = {09/2015}, pages = {305{\textendash}315}, abstract = {

The epigenetic effects of cytosine methylation on gene expression are an acknowledged source of phenotypic variance. The discordant monozygotic (MZ) twin design has been used to demonstrate the role of methylation in disease. Application of the classical twin design, featuring both monozygotic and dizygotic twins, has demonstrated that individual differences in methylation levels are attributable to genetic and environmental (including stochastic) factors, with the latter explaining most of the variance. What implications epigenetic sources of variance have for the twin modeling of (non-epigenetic) phenotypes such as height and IQ is an open question. One possibility is that epigenetic effects are absorbed by the variance component attributable to unshared environmental. Another possibility is that such effects form an independent source of variance distinguishable in principle from standard genetic and environmental sources. In the present paper, we conceptualized epigenetic processes as giving rise to randomness in the effects of polygenetic influences. This means that the regression coefficient in the regression of the phenotype on the polygenic factor, as specified in the twin model, varies over individuals. We investigate the consequences of ignoring this randomness in the standard twin model.

}, keywords = {classical twin design, epigenetics, heritability, methylation, parameter randomness}, doi = {http://dx.doi.org/10.2147/AGG.S46909}, url = {https://www.dovepress.com/methylation-as-an-epigenetic-source-of-random-genetic-effects-in-the-c-peer-reviewed-article-AGG}, author = {Conor V Dolan and Michel G. Nivard and Jenny van Dongen and van der Sluis,Sophie and Dorret I. Boomsma} }