期刊
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
卷 44, 期 2, 页码 496-511出版社
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyv071
关键词
Mendelian randomization; instrumental variable; aetiology
资金
- Netherlands Organisation for Health Research and Development ZonMw [152002040]
Background: Mendelian randomization (MR) studies investigate the effect of genetic variation in levels of an exposure on an outcome, thereby using genetic variation as an instrumental variable (IV). We provide a meta-epidemiological overview of the methodological approaches used in MR studies, and evaluate the discussion of MR assumptions and reporting of statistical methods. Methods: We searched PubMed, Medline, Embase and Web of Science for MR studies up to December 2013. We assessed (i) the MR approach used; (ii) whether the plausibility of MR assumptions was discussed; and (iii) whether the statistical methods used were reported adequately. Results: Of 99 studies using data from one study population, 32 used genetic information as a proxy for the exposure without further estimation, 44 performed a formal IV analysis, 7 compared the observed with the expected genotype-outcome association, and 1 used both the latter two approaches. The 80 studies using data from multiple study populations used many different approaches to combine the data; 52 of these studies used some form of IV analysis; 44% of studies discussed the plausibility of all three MR assumptions in their study. Statistical methods used for IV analysis were insufficiently described in 14% of studies. Conclusions: Most MR studies either use the genotype as a proxy for exposure without further estimation or perform an IV analysis. The discussion of underlying assumptions and reporting of statistical methods for IV analysis are frequently insufficient. Studies using data from multiple study populations are further complicated by the combination of data or estimates. We provide a checklist for the reporting of MR studies.
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