期刊
RESEARCH SYNTHESIS METHODS
卷 10, 期 4, 页码 486-496出版社
WILEY
DOI: 10.1002/jrsm.1346
关键词
Mendelian randomization; meta-analysis; pleiotropy; two-sample summary data MR
资金
- MRC [MC_UU_00011/2] Funding Source: UKRI
Mendelian randomization (MR) uses genetic variants as instrumental variables to infer whether a risk factor causally affects a health outcome. Meta-analysis has been used historically in MR to combine results from separate epidemiological studies, with each study using a small but select group of genetic variants. In recent years, it has been used to combine genome-wide association study (GWAS) summary data for large numbers of genetic variants. Heterogeneity among the causal estimates obtained from multiple genetic variants points to a possible violation of the necessary instrumental variable assumptions. In this article, we provide a basic introduction to MR and the instrumental variable theory that it relies upon. We then describe how random effects models, meta-regression, and robust regression are being used to test and adjust for heterogeneity in order to improve the rigor of the MR approach.
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