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Birth weight predicts psychiatric and physical health, cognitive function, and DNA methylation differences in an adult population

By Rebecca A Madden, Daniel L. McCartney, Rosie M. Walker, Robert F. Hillary, Mairead L. Bermingham, Konrad Rawlik, Stewart W Morris, Archie Campbell, David Porteous, Ian J. Deary, Kathryn L Evans, Jonathan Hafferty, Andrew M McIntosh, Riccardo E. Marioni

Posted 09 Jun 2019
bioRxiv DOI: 10.1101/664045

Introduction: The Developmental Origins of Adult Disease (DOAD) theory predicts that prenatal and early life events shape adult health outcomes. Birth weight is a useful indicator of the foetal experience, and has been associated with multiple adult health outcomes. DNA methylation (DNAm) is one plausible mechanism behind the relationship of birth weight to adult health. Methods: The Generation Scotland study purposefully oversampled individuals from three historic Scottish birth cohort studies containing birthweight information, and linked additional individuals to their birth records through the NHS Information and Statistics Division. Data linkage with these sources yielded a sample of 4,710 individuals. Health and disease measures were related to birth weight in regression models. An epigenome-wide association study (EWAS) was performed in a subgroup (n=1,395), relating adult DNAm to birth weight. Replication was assessed in an independent sample (n=362). Results: Higher birth weight was significantly associated with reduced incidence of depression, higher body mass index (BMI), lower risk of osteoarthritis, and higher general intelligence score (absolute standardised effect sizes ranged from 0.04 to 0.30, P(FDR)<0.05). Meta-analysis of the discovery and replication EWAS studies yielded one genome-wide significant CpG site (p=5.97×10−9), which was located in a gene linked to placental embedding. Conclusions: Our results demonstrate associations between birth weight and adult health and functional outcomes, with particularly striking effects for depression risk. It also provides support for an association between birth weight and DNAm. This study is the first to describe an EWAS of birth weight in an adult sample.

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