A robust and efficient method for Mendelian randomization with hundreds of genetic variants.,Nature Communications

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A robust and efficient method for Mendelian randomization with hundreds of genetic variants.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41467-019-14156-4
Stephen Burgess _{1,

2} , Christopher N Foley ₁ , Elias Allara _{2,

3} , James R Staley _{2,

4} , Joanna M M Howson _{2,

5,

6}

Affiliation

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.

中文翻译：

一种稳健且有效的孟德尔随机化方法，具有数百种遗传变异。

孟德尔随机化 (MR) 是一种流行病学技术，利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。我们开发了污染混合法，一种具有两种模式的 MR 方法。首先，它识别出具有相似因果估计的遗传变异组，这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 的情况下稳健且高效地执行 MR。与其他稳健的方法相比，它在一系列实际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升高、甘油三酯水平降低和冠心病风险降低相关的变异，这些变异与各种血细胞特征具有相同的关联方向，这表明血脂与冠心病风险介导的共同机制通过血小板聚集。

更新日期：2020-01-17

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