Wehby George L, Scholder Stephanie von Hinke Kessler
Department of Health Management and Policy, University of Iowa, Iowa City, IA, USA.
Biodemography Soc Biol. 2013;59(1):4-36. doi: 10.1080/19485565.2013.774615.
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.
识别孕期母亲风险因素对婴幼儿健康的影响是一个备受研究关注的领域。然而，政策制定者主要感兴趣的是理清产前风险因素的因果效应，而非它们与儿童健康的关联，因为这些关联可能会被一些未观察到的因素混淆。在本文中，我们评估了三个基因中的遗传变异作为识别孕期此类因素因果效应的工具变量的效用，这三个基因分别与吸烟、饮酒和肥胖这三个主要风险因素有明确的关联证据，即与吸烟相关的CHRNA3、与饮酒相关的ADH1B以及与肥胖相关的FTO。使用两个独立数据集，我们发现这些变异总体上可预测风险因素，且与观察到的混杂因素无系统关联，这表明它们可能是有用的工具变量。我们还发现了一些提示性证据，表明遗传效应在孕期比孕前更强。我们提供了一个实证例子，说明如何使用这些遗传变异作为工具来评估风险因素对出生体重的影响。最后，我们为考虑使用这些变异作为工具变量的研究人员提供了建议。
