title: 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.
authors.affiliation: Department of Health Management and Policy, University of Iowa, Iowa City, IA, USA. george-wehby@uiowa.edu
authors.forename: George L
authors.initials: GL
authors.lastname: Wehby
authors.forename: Stephanie von Hinke Kessler
authors.initials: Sv
authors.lastname: Scholder
mesh_terms: D000426:Alcohol Dehydrogenase; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics*; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001724:Birth Weight; D015992:Body Mass Index; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005787:Gene Frequency; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects; D008603:Mental Health; D009765:Obesity / Q000235:genetics*; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000235:genetics; D011506:Proteins; D011978:Receptors, Nicotinic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D012959:Socioeconomic Factors
chemical_list: D000426:Alcohol Dehydrogenase; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D011506:Proteins; D011978:Receptors, Nicotinic; C489332:ADH1B protein, human; C526492:FTO protein, human