Wehby George, Jugessur Astanand, Murray Jeffrey C, Moreno Lina, Wilcox Allen, Lie Rolv T
Assistant Professor, Dept. of Health Management and Policy, College of Public Health, University of Iowa, 200 Hawkins Drive, E205 GH, Iowa City, IA 52242 USA, ;
Health Serv Outcomes Res Methodol. 2011 Jul 1;11(1-2):54-78. doi: 10.1007/s10742-011-0071-9.
This study uses instrumental variable (IV) models with genetic instruments to assess the effects of maternal smoking on the child's risk of orofacial clefts (OFC), a common birth defect. The study uses genotypic variants in neurotransmitter and detoxification genes relateded to smoking as instruments for cigarette smoking before and during pregnancy. Conditional maximum likelihood and two-stage IV probit models are used to estimate the IV model. The data are from a population-level sample of affected and unaffected children in Norway. The selected genetic instruments generally fit the IV assumptions but may be considered "weak" in predicting cigarette smoking. We find that smoking before and during pregnancy increases OFC risk substantially under the IV model (by about 4-5 times at the sample average smoking rate). This effect is greater than that found with classical analytic models. This may be because the usual models are not able to consider self-selection into smoking based on unobserved confounders, or it may to some degree reflect limitations of the instruments. Inference based on weak-instrument robust confidence bounds is consistent with standard inference. Genetic instruments may provide a valuable approach to estimate the "causal" effects of risk behaviors with genetic-predisposing factors (such as smoking) on health and socioeconomic outcomes.
本研究使用带有基因工具的工具变量（IV）模型，以评估孕期吸烟对儿童患口面部裂隙（OFC，一种常见的出生缺陷）风险的影响。该研究使用与吸烟相关的神经递质和解毒基因中的基因型变异作为孕期及孕前吸烟的工具变量。采用条件最大似然法和两阶段IV概率模型来估计IV模型。数据来自挪威受影响和未受影响儿童的人群水平样本。所选的基因工具变量总体上符合IV假设，但在预测吸烟方面可能被认为“较弱”。我们发现在IV模型下，孕期及孕前吸烟会大幅增加患OFC的风险（在样本平均吸烟率下约增加4至5倍）。这一效应大于经典分析模型所发现的效应。这可能是因为常规模型无法考虑基于未观察到的混杂因素的吸烟自我选择，或者在某种程度上可能反映了工具变量的局限性。基于弱工具变量稳健置信区间的推断与标准推断一致。基因工具变量可能为估计具有遗传易感性因素（如吸烟）的风险行为对健康和社会经济结果的“因果”效应提供一种有价值的方法。
