Li S, Sesia M, Romano Y, Candès E, Sabatti C
Department of Statistics, Stanford University, Stanford, California 94305, USA.
Department of Data Sciences and Operations, University of Southern California, Los Angeles, California 90089, USA.
Biometrika. 2022 Sep;109(3):611-629. doi: 10.1093/biomet/asab055. Epub 2021 Nov 2.
This paper develops a method based on model-X knockoffs to find conditional associations that are consistent across environments, controlling the false discovery rate. The motivation for this problem is that large data sets may contain numerous associations that are statistically significant and yet misleading, as they are induced by confounders or sampling imperfections. However, associations replicated under different conditions may be more interesting. In fact, consistency sometimes provably leads to valid causal inferences even if conditional associations do not. While the proposed method is widely applicable, this paper highlights its relevance to genome-wide association studies, in which robustness across populations with diverse ancestries mitigates confounding due to unmeasured variants. The effectiveness of this approach is demonstrated by simulations and applications to the UK Biobank data.
本文提出了一种基于X模型仿样的方法,用于寻找在不同环境下一致的条件关联,并控制错误发现率。提出这个问题的动机是,大数据集可能包含大量在统计上显著但具有误导性的关联,因为它们是由混杂因素或抽样缺陷引起的。然而,在不同条件下复制的关联可能更有意义。事实上,即使条件关联不能证明因果关系,一致性有时也能证明导致有效的因果推断。虽然所提出的方法具有广泛的适用性,但本文强调了它与全基因组关联研究的相关性,在全基因组关联研究中,不同祖先群体之间的稳健性减轻了由于未测量变异而导致的混杂。通过模拟和对英国生物银行数据的应用,证明了该方法的有效性。