Mendelian randomisation in cardiovascular research: an introduction for clinicians.
Mendelian randomisation in cardiovascular research: an introduction for clinicians.
复制标题
心血管研究中的孟德尔随机化：临床医生的简介。
DOI：
10.1136/heartjnl-2016-310605
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Holmes MV
中科院分区：
文献类型：
--
作者：
Bennett DA;Holmes MV
了解生物标志物在心血管和其他疾病中的因果作用对于找到治疗和预防疾病的有效方法（包括药物疗法）至关重要。经典的观察性研究对生物标志物在疾病发展中可能发挥的作用提供了幼稚的估计。然而，此类研究很容易出现偏差。这与药物开发有直接关系，就好像药物靶标追踪非因果生物标志物一样，这可能会导致这些药物在 III 期随机对照试验中代价高昂的失败。为了更可靠地表明生物标志物在疾病发展中可能存在的因果作用，越来越多地使用孟德尔随机化研究，而大规模遗传数据的可用性促进了这一点。我们进行了叙述性回顾，以便为从事心血管研究的临床医生提供孟德尔随机化的实用性描述。我们描述了基本原理，并提供了孟德尔随机化方法和潜在局限性的基本描述。我们给出了文献中的例子，其中孟德尔随机化为药物发现提供了关键信息，包括预测疗效、告知靶标介导的不良反应以及为药物重新利用提供潜在的新证据。所提供的各种例子说明了孟德尔随机化对于优先考虑心血管研究药物靶点的重要性。
Understanding the causal role of biomarkers in cardiovascular and other diseases is crucial in order to find effective approaches (including pharmacological therapies) for disease treatment and prevention. Classical observational studies provide naïve estimates of the likely role of biomarkers in disease development; however, such studies are prone to bias. This has direct relevance for drug development as if drug targets track to non-causal biomarkers, this can lead to expensive failure of these drugs in phase III randomised controlled trials. In an effort to provide a more reliable indication of the likely causal role of a biomarker in the development of disease, Mendelian randomisation studies are increasingly used, and this is facilitated by the availability of large-scale genetic data. We conducted a narrative review in order to provide a description of the utility of Mendelian randomisation for clinicians engaged in cardiovascular research. We describe the rationale and provide a basic description of the methods and potential limitations of Mendelian randomisation. We give examples from the literature where Mendelian randomisation has provided pivotal information for drug discovery including predicting efficacy, informing on target-mediated adverse effects and providing potential new evidence for drug repurposing. The variety of the examples presented illustrates the importance of Mendelian randomisation in order to prioritise drug targets for cardiovascular research.
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