Department of Clinical Epidemiology, Department of Endocrinology and Metabolic Diseases, and Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands.
Department of Clinical Epidemiology, Department of Endocrinology and Metabolic Diseases, and Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands. Department of Clinical Epidemiology, Department of Endocrinology and Metabolic Diseases, and Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands.
Int J Epidemiol. 2015 Apr;44(2):496-511. doi: 10.1093/ije/dyv071. Epub 2015 May 6.
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.
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.
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.
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.
孟德尔随机化（MR）研究旨在探究遗传变异对暴露水平的影响，从而将遗传变异作为工具变量（IV）。我们对 MR 研究中使用的方法进行了元流行病学综述，并评估了对 MR 假设的讨论和统计方法的报告。
我们检索了截至 2013 年 12 月的 PubMed、Medline、Embase 和 Web of Science 中的 MR 研究。我们评估了（i）所使用的 MR 方法；（ii）是否讨论了 MR 假设的合理性；以及（iii）是否充分报告了所使用的统计方法。
在来自一个研究人群的 99 项研究中，有 32 项研究使用遗传信息作为暴露的替代指标而未进一步估计，44 项研究进行了正式的 IV 分析，7 项研究比较了观察到的与预期的基因型-结局关联，还有 1 项研究同时使用了后两种方法。在使用来自多个研究人群的数据的 80 项研究中，使用了许多不同的方法来组合数据；其中 52 项研究使用了某种形式的 IV 分析；44%的研究在其研究中讨论了所有三个 MR 假设的合理性。14%的研究中，IV 分析所使用的统计方法描述不足。
大多数 MR 研究要么使用基因型作为未进一步估计的暴露替代指标，要么进行 IV 分析。对基本假设的讨论和 IV 分析的统计方法报告往往不足。使用来自多个研究人群的数据的研究因数据或估计值的组合而变得更加复杂。我们提供了一份用于报告 MR 研究的检查表。
