Genetic analysis of selection bias in a natural experiment: Investigating in-utero famine effects on elevated body mass index in the Dutch Hunger Winter Families Study.

Autor: Zhou J; Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA., Indik CE; Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA., Kuipers TB; Department of Biomedical Data Sciences, Sequencing Analysis Support Core, Leiden University Medical Center, Leiden, The Netherlands., Li C; Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson St, Ann Arbor, MI 48104, USA.; Department of Epidemiology, School of Public Health, University of Michigan, 426 Thompson St, , Ann Arbor, MI 48104, USA.; Department of Epidemiology, School of Public Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.; Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.; Faculty of Health Sciences, University of Macau, Macao SAR, China., Nivard MG; Department of Biological Psychology, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands., Ryan CP; Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA., Tucker-Drob EM; Department of Psychology and Population Research Center, University of Texas at Austin, Austin, TX, USA., Taeubert MJ; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands., Wang S; Department of Biostatistics, Joseph P. Mailman School of Public Health, Columbia University, New York, NY, USA., Wang T; Department of Biostatistics, Joseph P. Mailman School of Public Health, Columbia University, New York, NY, USA., Conley D; Department of Sociology, Princeton University, Princeton, NJ, USA., Heijmans BT; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands., Lumey LH; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA., Belsky DW; Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Jazyk: angličtina
Zdroj: American journal of epidemiology [Am J Epidemiol] 2024 Oct 02. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1093/aje/kwae376
Abstrakt: Natural-experiment designs that compare survivors of in-utero famine exposure to unaffected controls suggest that in-utero undernutrition predisposes to development of obesity. However, birth rates drop dramatically during famines. Selection bias could arise if factors that contribute to obesity also protect fertility and/or fetal survival under famine conditions. We investigated this hypothesis using genetic analysis of a famine-exposed birth cohort. We genotyped participants in the Dutch Hunger Winter Families Study (DHWFS, N=950; 45% male), of whom 51% were exposed to the 1944-1945 Dutch Famine during gestation and 49% were their unexposed same-sex siblings or "time controls" born before or after the famine in the same hospitals. We computed body-mass index (BMI) polygenic indices (PGIs) in DHWFS participants and compared BMI PGIs between famine-exposed and control groups. Participants with higher polygenic risk had higher BMIs (Pearson r=0.42, p<0.001). However, differences between BMI PGIs of famine-exposed participants and controls were small and not statistically different from zero across specifications (Cohen's d=0.10, p>0.092). Our findings did not indicate selection bias, supporting the validity of the natural-experiment design within DHWFS. In summary, our study outlines a novel approach to explore the presence of selection bias in famine and other natural experiment studies.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze: MEDLINE