Genetic Meta-Analysis of Twin Birth Weight Shows High Genetic Correlation with Singleton Birth Weight

Jeffrey J Beck, René Pool, Margot van de Weijer, Xu Chen, Eva Krapohl, Scott D Gordon, Marianne Nygaard, Birgit Debrabant, Teemu Palviainen, Matthijs D van der Zee, Bart Baselmans, Casey T Finnicum, Lu Yi, Sebastian Lundström, Toos van Beijsterveldt, Lene Christiansen, Kauko Heikkilä, Julie Kittelsrud, Anu Loukola, Miina OllikainenKaare Christensen, Nicholas G Martin, Robert Plomin, Michel Nivard, Meike Bartels, Conor Dolan, Gonneke Willemsen, Eco de Geus, Catarina Almqvist, Patrik K E Magnusson, Hamdi Mbarek, Erik A Ehli, Dorret I Boomsma, Jouke-Jan Hottenga

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Birth weight (BW) is an important predictor of newborn survival and health and has associations with many adult health outcomes, including cardio-metabolic 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'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 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.

Original languageEnglish
JournalHuman Molecular Genetics
Volume30
Issue number19
Pages (from-to)1894-1905
ISSN0964-6906
DOIs
Publication statusPublished - 15. Sep 2021

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