Credible Mendelian Randomization Studies: Approaches for Evaluating the Instrumental Variable Assumptions
Credible Mendelian Randomization Studies: Approaches for Evaluating the Instrumental Variable Assumptions
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DOI：
10.1093/aje/kwr323
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发表时间：
2012-02-15
影响因子：
5
通讯作者：
Robins, James M.
中科院分区：
文献类型：
--
作者：
Glymour, M. Maria;Tchetgen, Eric J. Tchetgen;Robins, James M.
与其他工具变量（IV）分析一样，孟德尔随机化（MR）研究依赖于强有力的假设。这些假设在MR应用中没有进行常规的系统评价，尽管这样的评价可以增加MR分析的可信度。在这篇文章中，作者提出了几种方法，用于评估MR研究的有效性。他们将这些方法应用于最近的MR研究，该研究使用脂肪量和肥胖相关（FTO）基因型作为IV来估计肥胖对精神障碍的影响。这些评估有效IV分析假设的方法并不安全，因为在某些情况下，这些方法可能无法识别有偏倚的IV或不适当地暗示有效IV存在偏倚。因此，作者描述了IV评估所依赖的假设。他们描述的方法与任何IV分析相关，无论它是基于遗传IV还是其他可能的外源变异来源。评估IV假设的方法通常不是结论性的，但常规应用这些方法可能会提高MR研究的科学贡献。
As with other instrumental variable (IV) analyses, Mendelian randomization (MR) studies rest on strong assumptions. These assumptions are not routinely systematically evaluated in MR applications, although such evaluation could add to the credibility of MR analyses. In this article, the authors present several methods that are useful for evaluating the validity of an MR study. They apply these methods to a recent MR study that used fat mass and obesity-associated (FTO) genotype as an IV to estimate the effect of obesity on mental disorder. These approaches to evaluating assumptions for valid IV analyses are not fail-safe, in that there are situations where the approaches might either fail to identify a biased IV or inappropriately suggest that a valid IV is biased. Therefore, the authors describe the assumptions upon which the IV assessments rely. The methods they describe are relevant to any IV analysis, regardless of whether it is based on a genetic IV or other possible sources of exogenous variation. Methods that assess the IV assumptions are generally not conclusive, but routinely applying such methods is nonetheless likely to improve the scientific contributions of MR studies.