MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Int J Epidemiol. 2023 Apr 19;52(2):536-544. doi: 10.1093/ije/dyac165.
Mendelian randomization (MR) is a form of instrumental variable analysis used to investigate causality using observational data. Another important, although less frequently applied, use of this technique is to investigate confounding due to reverse causality.
We used a form of reverse MR and data from UK Biobank in a proof-of-principle study to investigate confounding due to reverse causation. Here we focus on the association between alcohol consumption (exposure) and outcomes including educational attainment, and physical and mental health. First, we examined the observational relationship between alcohol consumption and these outcomes. Allele scores were then derived for educational attainment, and physical and mental health, and the association with alcohol consumption (as the outcome) was explored. Sample sizes ranged from 114 941-336 473 in observational analyses and 142 093-336 818 in genetic analyses.
Conventional observational analyses indicated associations between alcohol consumption and a number of outcomes (e.g. neuroticism, body mass index, educational attainment). Analyses using allele scores suggested evidence of reverse causation for several of these relationships (in particular physical health and educational attainment).
Allele scores allow us to investigate reverse causation in observational studies. Our findings suggest that observed associations implying beneficial effects of alcohol consumption may be due to confounding by reverse causation in many cases.
孟德尔随机化（MR）是一种工具变量分析形式，用于使用观察数据研究因果关系。这种技术的另一个重要但应用较少的用途是研究由于反向因果关系引起的混杂。
我们使用反向 MR 的一种形式和来自英国生物库的数据，在一项原理验证研究中，研究由于反向因果关系引起的混杂。在这里，我们专注于饮酒（暴露）与包括教育程度、身体和心理健康在内的结果之间的关联。首先，我们检查了饮酒与这些结果之间的观察性关系。然后为教育程度和身心健康推导了等位基因分数，并探讨了它们与饮酒（作为结果）的关联。观察性分析的样本量范围为 114941-336473，遗传分析的样本量范围为 142093-336818。
常规观察性分析表明，饮酒与许多结果之间存在关联（例如神经质、体重指数、教育程度）。使用等位基因分数的分析表明，这些关系中的几个关系存在反向因果关系的证据（特别是身体健康和教育程度）。
等位基因分数使我们能够在观察性研究中研究反向因果关系。我们的研究结果表明，在许多情况下，观察到的饮酒有益效果的关联可能是由于反向因果关系引起的混杂。
