论文标题
使用仪器进行选择以调整孟德尔随机化中的选择偏差
Using Instruments for Selection to Adjust for Selection Bias in Mendelian Randomization
论文作者
论文摘要
选择偏见是流行病学研究中的普遍关注点。在文献中,选择偏差通常被视为缺失的数据问题。由于缺少数据而引起的偏差的流行方法(例如逆概率加权)取决于以下假设:数据是随机丢失的,如果违反了此假设,则会产生偏见的结果。在观察性研究并非随机缺失的结果数据中,由于缺少数据,Heckman的样本选择模型可用于调整偏差。在本文中,我们回顾了Heckman的方法以及Tchetgen Tchetgen和Wirth(2017)提出的类似方法。然后,我们讨论如何使用单个级别的数据将这些方法应用于门德尔随机分析,而缺少有关暴露或结果或两者兼而有之的数据。我们探索是否可以将与参与相关的遗传变异用作选择的工具。然后,我们描述了如何获得经过调整的WALD比率,两个阶段最小二乘和反向方差加权估计值。在模拟中评估和比较了这两种方法,结果表明它们既可以减轻选择偏差,又可能在某些设置中产生大标准误差的参数估计。在说明性的真实数据应用中,我们使用父母和孩子的雅芳纵向研究研究了体重指数对吸烟的影响。
Selection bias is a common concern in epidemiologic studies. In the literature, selection bias is often viewed as a missing data problem. Popular approaches to adjust for bias due to missing data, such as inverse probability weighting, rely on the assumption that data are missing at random and can yield biased results if this assumption is violated. In observational studies with outcome data missing not at random, Heckman's sample selection model can be used to adjust for bias due to missing data. In this paper, we review Heckman's method and a similar approach proposed by Tchetgen Tchetgen and Wirth (2017). We then discuss how to apply these methods to Mendelian randomization analyses using individual-level data, with missing data for either the exposure or outcome or both. We explore whether genetic variants associated with participation can be used as instruments for selection. We then describe how to obtain missingness-adjusted Wald ratio, two-stage least squares and inverse variance weighted estimates. The two methods are evaluated and compared in simulations, with results suggesting that they can both mitigate selection bias but may yield parameter estimates with large standard errors in some settings. In an illustrative real-data application, we investigate the effects of body mass index on smoking using data from the Avon Longitudinal Study of Parents and Children.