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

doi:10.1038/s41467-020-19257-z

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 journal › Article (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 language	English
Article number	5404 (2020)
Number of pages	12
Journal	Nature Communications
Volume	11
DOIs	https://doi.org/10.1038/s41467-020-19257-z
Publication status	Published - 26 Oct 2020

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8073 MRC IEU - Programme 6
Lawlor, D. A. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research
IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

Professor Debbie A Lawlor
- D.A.Lawlorbristol.acuk
- Bristol Medical School (PHS) - Professor of Epidemiology, MRC Investigator and BHF Chair
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
Person: Academic , Member

Cite this

Moen, G.-H., Brumpton, B. M., Willer, C. J., Asvold, B. O., Birkeland, K. I., Wale, G., Neale, M., Freathy, R. M., Davey Smith, G., Lawlor, D. A., Kirkpatrick, R. M., Warrington, N. M., & Evans, D. (2020). Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort. Nature Communications, 11, Article 5404 (2020). https://doi.org/10.1038/s41467-020-19257-z

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

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-Tr{\o}ndelag 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.",

author = "Gunn-Helen Moen and Brumpton, {Ben M} and Willer, {Cristen J} and Asvold, {Bj{\o}rn Olav} and Birkeland, {K{\aa}re I.} and Geng Wale and Michael Neale and Freathy, {Rachel M} and {Davey Smith}, George and Lawlor, {Debbie A} and Kirkpatrick, {Robert M} and Warrington, {Nicole M} and David Evans",

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month = oct,

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doi = "10.1038/s41467-020-19257-z",

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Moen, G-H, Brumpton, BM, Willer, CJ, Asvold, BO, Birkeland, KI, Wale, G, Neale, M, Freathy, RM, Davey Smith, G , Lawlor, DA, Kirkpatrick, RM, Warrington, NM & Evans, D 2020, 'Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort', Nature Communications, vol. 11, 5404 (2020). https://doi.org/10.1038/s41467-020-19257-z

TY - JOUR

T1 - Mendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort

AU - Moen, Gunn-Helen

AU - Brumpton, Ben M

AU - Willer, Cristen J

AU - Asvold, Bjørn Olav

AU - Birkeland, Kåre I.

AU - Wale, Geng

AU - Neale, Michael

AU - Freathy, Rachel M

AU - Davey Smith, George

AU - Lawlor, Debbie A

AU - Kirkpatrick, Robert M

AU - Warrington, Nicole M

AU - Evans, David

PY - 2020/10/26

Y1 - 2020/10/26

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-19257-z

DO - 10.1038/s41467-020-19257-z

M3 - Article (Academic Journal)

C2 - 33106479

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

M1 - 5404 (2020)

ER -

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

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Projects

8073 MRC IEU - Programme 6

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

Profiles

Professor Debbie A Lawlor

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