Elucidating the role of maternal environmental exposures on offspring health and disease using two-sample Mendelian randomization.

International Journal of Epidemiology
David M EvansNicole M Warrington

Abstract

There is considerable interest in estimating the causal effect of a range of maternal environmental exposures on offspring health-related outcomes. Previous attempts to do this using Mendelian randomization methodologies have been hampered by the paucity of epidemiological cohorts with large numbers of genotyped mother-offspring pairs. We describe a new statistical model that we have created which can be used to estimate the effect of maternal genotypes on offspring outcomes conditional on offspring genotype, using both individual-level and summary-results data, even when the extent of sample overlap is unknown. We describe how the estimates obtained from our method can subsequently be used in large-scale two-sample Mendelian randomization studies to investigate the causal effect of maternal environmental exposures on offspring outcomes. This includes studies that aim to assess the causal effect of in utero exposures related to fetal growth restriction on future risk of disease in offspring. We illustrate our framework using examples related to offspring birthweight and cardiometabolic disease, although the general principles we espouse are relevant for many other offspring phenotypes. We advocate for the establishment of large...Continue Reading

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Citations

Jul 22, 2019·International Journal of Epidemiology·Stephen Burgess, George Davey Smith
Oct 28, 2019·Human Molecular Genetics·Neil M DaviesGeorge Davey Smith
Aug 12, 2020·Paediatric and Perinatal Epidemiology·Elizabeth W DiemerSonja A Swanson
Aug 23, 2020·International Journal of Molecular Sciences·Sabrina I HanswijkJudith R Homberg
Dec 5, 2020·Journal of Developmental Origins of Health and Disease·Shannon D'UrsoDavid M Evans
Dec 22, 2020·International Journal of Epidemiology·Gunn-Helen MoenNicole M Warrington
Jan 3, 2021·Behavior Genetics·Jared V BalbonaMatthew C Keller
Jan 3, 2021·Behavior Genetics·Espen Moen EilertsenEivind Ystrom
Jan 10, 2021·NPJ Science of Learning·Sara A HartElsje van Bergen
Mar 4, 2020·Cold Spring Harbor Perspectives in Medicine·Liang-Dar HwangDavid M Evans
Feb 22, 2021·European Journal of Epidemiology·Stephen BurgessJeremy A Labrecque
Apr 18, 2021·Behavior Genetics·David M EvansElizabeth Prom-Wormley
Jun 29, 2021·Journal of Developmental Origins of Health and Disease·Carlos Sánchez-SorianoRebecca M Reynolds
May 7, 2021·Human Molecular Genetics·Jeffrey J BeckJouke-Jan Hottenga
Dec 2, 2021·The Journal of Clinical Endocrinology and Metabolism·Yuexin GanJian Zhao
Aug 25, 2021·Cold Spring Harbor Perspectives in Medicine·Rebecca C Richmond, George Davey Smith

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Methods Mentioned

BETA
genotyping

Software Mentioned

R
DevelopObese
OpenMx
DOHaD

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