Journal article

Diagnostics for Pleiotropy in Mendelian Randomization Studies: Global and Individual Tests for Direct Effects

James Y Dai, Ulrike Peters, Xiaoyu Wang, Jonathan Kocarnik, Jenny Chang-Claude, Martha L Slattery, Andrew Chan, Mathieu Lemire, Sonja I Berndt, Graham Casey, Mingyang Song, Mark A Jenkins, Hermann Brenner, Aaron P Thrift, Emily White, Li Hsu

AMERICAN JOURNAL OF EPIDEMIOLOGY | OXFORD UNIV PRESS INC | Published : 2018

Abstract

Diagnosing pleiotropy is critical for assessing the validity of Mendelian randomization (MR) analyses. The popular MR-Egger method evaluates whether there is evidence of bias-generating pleiotropy among a set of candidate genetic instrumental variables. In this article, we propose a statistical method-global and individual tests for direct effects (GLIDE)-for systematically evaluating pleiotropy among the set of genetic variants (e.g., single nucleotide polymorphisms (SNPs)) used for MR. As a global test, simulation experiments suggest that GLIDE is nearly uniformly more powerful than the MR-Egger method. As a sensitivity analysis, GLIDE is capable of detecting outliers in individual variant..

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