Journal Article

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

Birkeland, Kåre I., Åsvold, Bjørn Olav, Neale, Michael C., Lawlor, Deborah A., Brumpton, Ben, Moen, Gunn-Helen, Smith, George Davey, Wang, Geng, Freathy, Rachel M., Willer, Cristen, Kirkpatrick, Robert M., Evans, David M., Warrington, Nicole M.

2020

Overview

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. Observationally, lower birthweight is a risk factor for cardiometabolic disease. Using Mendelian Randomization, the authors investigate whether maternal genetic factors that lower offspring birthweight also increase offspring cardiometabolic risk and show that the observational correlation is unlikely to be due to the intrauterine environment.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/208/205 / 692/308/174 / 692/308/2056 / 692/499 / Adult / Birth Weight / Cardiovascular Diseases - epidemiology / Cardiovascular Diseases - genetics / Cardiovascular Diseases - physiopathology / Cohort Studies / Environmental factors / Female / Genetic factors / Health risk assessment / Health risks / Humanities and Social Sciences / Humans / Infant, Newborn / Intrauterine exposure / Male / Maternal Inheritance / Mendelian Randomization Analysis / multidisciplinary / Norway - epidemiology / Offspring / Paternal Inheritance / Polymorphism, Single Nucleotide / Randomization / Risk analysis / Risk Factors / Risk management / Science / Science (multidisciplinary) / Single-nucleotide polymorphism / Young Adult