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

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

doi:10.1038/s41467-020-19257-z

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

Nat Commun. 2020 Oct 26;11(1):5404. doi: 10.1038/s41467-020-19257-z.

Authors

Gunn-Helen Moen^{1

2

3

4}, Ben Brumpton^{5

6

7}, Cristen Willer^{8

9

10}, Bjørn Olav Åsvold^{5

11}, Kåre I Birkeland¹², Geng Wang¹³, Michael C Neale¹⁴, Rachel M Freathy¹⁵, George Davey Smith^{16

7

17}, Deborah A Lawlor^{16

7

17}, Robert M Kirkpatrick¹⁴, Nicole M Warrington^{13

5

7}, David M Evans^{18

19}

Affiliations

¹ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. g.h.moen@medisin.uio.no.
² The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia. g.h.moen@medisin.uio.no.
³ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. g.h.moen@medisin.uio.no.
⁴ Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK. g.h.moen@medisin.uio.no.
⁵ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
⁶ Department of Thoracic and Occupational Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
⁷ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
⁸ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, USA.
⁹ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
¹¹ Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
¹² Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹³ The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia.
¹⁴ Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
¹⁵ Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, UK.
¹⁶ Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
¹⁷ Bristol NIHR Biomedical Research Centre, Bristol, UK.
¹⁸ The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia. d.evans1@uq.edu.au.
¹⁹ Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. d.evans1@uq.edu.au.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Birth Weight*
Cardiovascular Diseases / epidemiology
Cardiovascular Diseases / genetics*
Cardiovascular Diseases / physiopathology
Cohort Studies
Female
Humans
Infant, Newborn
Male
Maternal Inheritance*
Mendelian Randomization Analysis
Norway / epidemiology
Paternal Inheritance
Polymorphism, Single Nucleotide
Risk Factors
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding