Genetic instrumental variable studies of effects of prenatal risk factors

Abstract

Identifying the effects of maternal risk factors during pregnancy on infant and child health is an area of tremendous research interest. However, policymakers are primarily interested in unraveling the causal effects of prenatal risk factors, not their associations with child health, which may be confounded by several unobserved factors. In this article, we evaluate the utility of genetic variants in three genes that have unequivocal evidence of being related to three major risk factors - CHRNA3 for smoking, ADH1B for alcohol use, and FTO for obesity - as instrumental variables for identifying the causal effects of such factors during pregnancy. Using two independent datasets, we find that these variants are overall predictive of the risk factors and are not systematically related to observed confounders, suggesting that they may be useful instruments. We also find some suggestive evidence that genetic effects are stronger during than before pregnancy. We provide an empirical example illustrating the use of these genetic variants as instruments to evaluate the effects of risk factors on birth weight. Finally, we offer suggestions for researchers contemplating the use of these variants as instruments. Data analysis of the DNBC dataset was supported by NIH/NIDCR grant 1 R01 DE020895. We are extremely grateful to all the families who took part in the DNBC and ALSPAC studies; the staff and midwives for their help in recruiting them; and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. The UK Medical Research Council, the Wellcome Trust, and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and does not reflect the views of the ALSPAC executive. We thank Drs. Mads Melbye and Jeffrey C. Murray for providing access to the DNBC data. We also thank Dr. Bjarke Feenstra for his thoughtful review of the paper. Copyright © Society for Biodemography and Social Biology.