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Instrumental Variable Analysis in Underrepresented Subpopulations Powered by Knowledge Transfer

借助知识迁移增强代表性不足子群体的工具变量分析

Instrumental variable (IV) analysis in underrepresented target populations suffers from low statistical efficiency and weak IV bias due to limited sample size. Leveraging external knowledge from a source population with larger samples offers an appealing solution to this problem. We propose in this paper the KNowledge-powered IV Estimator for underrepresented Subpopulations (KNIVES), a framework that enhances the IV analysis for underrepresented subpopulations by…

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Debiased Estimating Equation Method for Robust and Efficient Mendelian Randomization Using a Large Number of Correlated Weak and Invalid Instruments

使用大量相关弱工具和无效工具的稳健有效孟德尔随机化:去偏估计方程法

Mendelian randomization (MR) is a widely used tool for causal inference in the presence of unmeasured confounders, which uses single nucleotide polymorphisms (SNPs) as instrumental variables to estimate causal effects. However, SNPs often have weak effects on complex traits, leading to bias in existing MR analysis when weak instruments are included. In addition, existing MR methods often restrict analysis to independent SNPs via linkage disequilibrium clumping and result in…

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Testing a Large Number of Composite Null Hypotheses Using Conditionally Symmetric Multidimensional Gaussian Mixtures in Genome-Wide Studies

全基因组研究中基于条件对称多维高斯混合的大规模复合零假设检验

Causal mediation analysis, pleiotropy analysis, and replication analysis are three highly popular genetic study designs. Although these analyses address different scientific questions, the underlying inference problems all involve large-scale testing of composite null hypotheses. The goal is to determine whether all null hypotheses - as opposed to at least one - in a set of individual tests should simultaneously be rejected. Various recent methodology has been proposed for…

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