MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Mol Psychiatry. 2022 Jan;27(1):53-57. doi: 10.1038/s41380-021-01173-3. Epub 2021 Jun 4.
The successful prevention of mental illness relies upon the identification of causal, modifiable risk factors. However, observational evidence exploring such risk factors often produces contradictory results and randomised control trials are often expensive, time-consuming or unethical to conduct. Mendelian randomisation (MR) is a complementary approach that uses naturally occurring genetic variation to identify possible causal effects between a risk factor and an outcome in a time-efficient and low-cost manner. MR utilises genetic variants as instrumental variables for the risk factor of interest. MR studies are becoming more frequent in the field of psychiatry, warranting a reflection upon both the possibilities and the pitfalls. In this Perspective, we consider several limitations of the MR method that are of particular relevance to psychiatry. We also present new MR methods that have exciting applications to questions of mental illness. While we believe that MR can make an important contribution to the field of psychiatry, we also wish to emphasise the importance of clear causal questions, thorough sensitivity analyses, and triangulation with other forms of evidence.
成功预防精神疾病依赖于识别因果可调节风险因素。然而，观察性证据经常产生相互矛盾的结果，并且随机对照试验往往昂贵、耗时或不道德。孟德尔随机化（MR）是一种补充方法，它利用自然发生的遗传变异，以高效和低成本的方式识别风险因素与结果之间可能的因果关系。MR 将遗传变异用作感兴趣的风险因素的工具变量。MR 研究在精神病学领域越来越频繁，因此有必要对其可能性和陷阱进行反思。在本文中，我们考虑了 MR 方法对精神病学特别相关的几个局限性。我们还介绍了新的 MR 方法，这些方法对精神疾病的问题具有令人兴奋的应用。虽然我们认为 MR 可以为精神病学领域做出重要贡献，但我们也希望强调提出明确的因果问题、进行彻底的敏感性分析以及与其他形式的证据进行三角验证的重要性。
