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

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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'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.

Original languageEnglish
Pages (from-to)1894-1905
Number of pages12
JournalHuman molecular genetics
Volume30
Issue number19
Early online date6 May 2021
DOIs
Publication statusPublished - 1 Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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