A robust and efficient method for Mendelian randomization with hundreds of genetic variants
A robust and efficient method for Mendelian randomization with hundreds of genetic variants
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DOI：
10.1038/s41467-019-14156-4
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发表时间：
2020-01-17
影响因子：
16.6
通讯作者：
Howson, Joanna M. M.
中科院分区：
文献类型：
--
作者：
Burgess, Stephen;Foley, Christopher N.;Howson, Joanna M. M.
孟德尔随机化（MR）是一种流行病学技术，它使用遗传变异来区分观察数据中的相关性和因果关系。MR研究的可靠性取决于遗传变异作为工具变量（IV）的有效性。我们开发的污染混合物的方法，MR的方法与两种模式。首先，它确定了具有相似因果估计的遗传变异组，这些遗传变异组可能代表风险因素影响结果的不同机制。其次，它在存在无效IV的情况下稳健有效地执行MR。与其他鲁棒方法相比，它在一系列现实场景中具有最低的均方误差。该方法鉴定了11种与高密度脂蛋白胆固醇增加、甘油三酯水平降低和冠心病风险降低相关的变体，这些变体与各种血细胞性状具有相同的关联方向，表明通过血小板聚集介导的脂质和冠心病风险之间存在共同的机制。
Mendelian randomization (MR) is an epidemiological technique that uses genetic variants to distinguish correlation from causation in observational data. The reliability of a MR investigation depends on the validity of the genetic variants as instrumental variables (IVs). We develop the contamination mixture method, a method for MR with two modalities. First, it identifies groups of genetic variants with similar causal estimates, which may represent distinct mechanisms by which the risk factor influences the outcome. Second, it performs MR robustly and efficiently in the presence of invalid IVs. Compared to other robust methods, it has the lowest mean squared error across a range of realistic scenarios. The method identifies 11 variants associated with increased high-density lipoprotein-cholesterol, decreased triglyceride levels, and decreased coronary heart disease risk that have the same directions of associations with various blood cell traits, suggesting a shared mechanism linking lipids and coronary heart disease risk mediated via platelet aggregation.