Genetic instrumental variable studies of effects of prenatal risk factors.
Genetic instrumental variable studies of effects of prenatal risk factors.
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DOI：
10.1080/19485565.2013.774615
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发表时间：
2013
影响因子：
1.3
通讯作者：
Scholder Sv
中科院分区：
文献类型：
--
作者：
Wehby GL;Scholder Sv
确定怀孕期间产妇的危险因素对婴儿和儿童健康的影响是一个巨大的研究兴趣的领域。然而，政策制定者感兴趣的是解开产前风险因素的因果关系，而不是它们与儿童健康的关系，这可能会被一些未观察到的因素所混淆。在本文中，我们评估了三个基因中遗传变异的效用，这些基因有明确的证据表明与三个主要风险因素相关-吸烟的CHRNA 3，饮酒的ADH 1B和肥胖的FTO-作为识别这些因素在怀孕期间的因果影响的工具变量。使用两个独立的数据集，我们发现，这些变量是整体预测的风险因素，并没有系统地与观察到的混杂因素，这表明他们可能是有用的工具。我们还发现了一些暗示性的证据，表明遗传效应在怀孕期间比怀孕前更强。我们提供了一个实证的例子，说明使用这些遗传变异的工具，以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体作为工具的研究人员提供了建议。
Identifying the effects of maternal risk factors during pregnancy on infant and child health is an area of tremendous research interest. However, of interest to policy makers is unraveling the causal effects of prenatal risk factors, not their associations with child health, which may be confounded by several unobserved factors. In this paper, 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.
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