期刊
STATISTICS IN MEDICINE
卷 36, 期 11, 页码 1783-1802出版社
WILEY
DOI: 10.1002/sim.7221
关键词
instrumental variables; Mendelian randomization; meta-analysis; MR-Egger regression; pleiotropy
类别
资金
- MRC Methodology Research Fellowship [MR/N501906/1]
- MRC Integrative Epidemiology Unit at the University of Bristol [MCUU12013/1]
- Medical Research Council [MR/N501906/1, MC_UU_12013/1, MC_UU_12013/9, MC_EX_MR/L012286/1] Funding Source: researchfish
- MRC [MC_UU_12013/1, MC_EX_MR/L012286/1, MC_UU_12013/9] Funding Source: UKRI
Mendelian randomization (MR) uses genetic data to probe questions of causality in epidemiological research, by invoking the Instrumental Variable (IV) assumptions. In recent years, it has become commonplace to attempt MR analyses by synthesising summary data estimates of genetic association gleaned from large and independent study populations. This is referred to as two-sample summary data MR. Unfortunately, due to the sheer number of variants that can be easily included into summary data MR analyses, it is increasingly likely that some do not meet the IV assumptions due to pleiotropy. There is a pressing need to develop methods that can both detect and correct for pleiotropy, in order to preserve the validity of the MR approach in this context. In this paper, we aim to clarify how established methods of meta-regression and random effects modelling from mainstream meta-analysis are being adapted to perform this task. Specifically, we focus on two contrasting approaches: the Inverse Variance Weighted (IVW) method which assumes in its simplest form that all genetic variants are valid IVs, and the method of MR-Egger regression that allows all variants to violate the IV assumptions, albeit in a specific way. We investigate the ability of two popular random effects models to provide robustness to pleiotropy under the IVW approach, and propose statistics to quantify the relative goodness-of-fit of the IVW approach over MR-Egger regression. (C) 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd
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