Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort

Gunn-Helen Moen*, Ben M Brumpton, Cristen J Willer, Bjørn Olav Asvold, Kåre I. Birkeland, Geng Wale, Michael Neale, Rachel M Freathy, George Davey Smith, Debbie A Lawlor, Robert M Kirkpatrick, Nicole M Warrington, David Evans*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

There is a robust observational relationship between lower birthweight and higher risk of cardiometabolic disease in later life. The Developmental Origins of Health and Disease (DOHaD) hypothesis posits that adverse environmental factors in utero increase future risk of cardiometabolic disease. Here, we explore if a genetic risk score (GRS) of maternal SNPs associated with offspring birthweight is also associated with offspring cardiometabolic risk factors, after controlling for offspring GRS, in up to 26,057 mother–offspring pairs (and 19,792 father–offspring pairs) from the Nord-Trøndelag Health (HUNT) Study. We find little evidence for a maternal (or paternal) genetic effect of birthweight associated variants on offspring cardiometabolic risk factors after adjusting for offspring GRS. In contrast, offspring GRS is strongly related to many cardiometabolic risk factors, even after conditioning on maternal GRS. Our results suggest that the maternal intrauterine environment, as proxied by maternal SNPs that influence offspring birthweight, is unlikely to be a major determinant of adverse cardiometabolic outcomes in population based samples of individuals.
Original languageEnglish
Article number5404 (2020)
Number of pages12
JournalNature Communications
Volume11
DOIs
Publication statusPublished - 26 Oct 2020

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