Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.
Cardiovasc Res. 2018 Jul 15;114(9):1192-1208. doi: 10.1093/cvr/cvy045.
The Mendelian randomization approach is an epidemiological study design incorporating genetic information into traditional epidemiological studies to infer causality of biomarkers, risk factors, or lifestyle factors on disease risk. Mendelian randomization studies often draw on novel information generated in genome-wide association studies on causal associations between genetic variants and a risk factor or lifestyle factor. Such information can then be used in a largely unconfounded study design free of reverse causation to understand if and how risk factors and lifestyle factors cause cardiovascular disease. If causation is demonstrated, an opportunity for prevention of disease is identified; importantly however, before prevention or treatment can be implemented, randomized intervention trials altering risk factor levels or improving deleterious lifestyle factors needs to document reductions in cardiovascular disease in a safe and side-effect sparse manner. Documentation of causality can also inform on potential drug targets, more likely to be successful than prior approaches often relying on animal or cell studies mainly. The present review summarizes the history and background of Mendelian randomization, the study design, assumptions for using the design, and the most common caveats, followed by a discussion on advantages and disadvantages of different types of Mendelian randomization studies using one or more samples and different levels of information on study participants. The review also provides an overview of results on many of the risk factors and lifestyle factors for cardiovascular disease examined to date using the Mendelian randomization study design.
孟德尔随机化方法是一种将遗传信息纳入传统流行病学研究以推断生物标志物、风险因素或生活方式因素与疾病风险之间因果关系的流行病学研究设计。孟德尔随机化研究通常利用全基因组关联研究中关于遗传变异与风险因素或生活方式因素之间因果关系的新信息。然后，可以在很大程度上不受反向因果关系影响的无偏设计中使用这些信息，以了解风险因素和生活方式因素是否以及如何导致心血管疾病。如果证明存在因果关系，则确定了预防疾病的机会；然而，在可以实施预防或治疗之前，需要改变风险因素水平或改善有害生活方式因素的随机干预试验以安全且副作用稀少的方式记录心血管疾病的减少。因果关系的证明还可以为潜在的药物靶点提供信息，这些靶点比以前通常依赖于动物或细胞研究的方法更有可能成功。本综述总结了孟德尔随机化的历史和背景、研究设计、使用设计的假设以及最常见的注意事项，然后讨论了使用一个或多个样本和不同水平的研究参与者信息的不同类型的孟德尔随机化研究的优缺点。该综述还概述了迄今为止使用孟德尔随机化研究设计对许多心血管疾病风险因素和生活方式因素进行的研究结果。
