期刊
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
卷 48, 期 3, 页码 713-727出版社
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyy262
关键词
Mendelian randomization; two-sample Mendelian randomization; multivariable Mendelian randomization; Cochran's Q statistic; instrument strength; instrument validity
资金
- UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol [MC_UU_00011/2, MC_UU_00011/1]
- MRC [MC_UU_00011/1, MC_UU_00011/2] Funding Source: UKRI
Background: Mendelian randomization (MR) is a powerful tool in epidemiology that can be used to estimate the causal effect of an exposure on an outcome in the presence of unobserved confounding, by utilizing genetic variants that are instrumental variables (IVs) for the exposure. This has been extended to multivariable MR (MVMR) to estimate the effect of two or more exposures on an outcome. Methods and results: We use simulations and theory to clarify the interpretation of estimated effects in a MVMR analysis under a range of underlying scenarios, where a secondary exposure acts variously as a confounder, a mediator, a pleiotropic pathway and a collider. We then describe how instrument strength and validity can be assessed for an MVMR analysis in the single-sample setting, and develop tests to assess these assumptions in the popular two-sample summary data setting. We illustrate our methods using data from UK Biobank to estimate the effect of education and cognitive ability on body mass index. Conclusion: MVMR analysis consistently estimates the direct causal effect of an exposure, or exposures, of interest and provides a powerful tool for determining causal effects in a wide range of scenarios with either individual- or summary-level data.
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