Using Mendelian randomization to evaluate the effects of alcohol consumption on the risk of coronary heart disease

Abstract

Purpose This paper aims to evaluate the use of Mendelian randomization (MR) analyses for judging the effects of alcohol consumption on the risk of coronary heart disease (CHD). Design/methodology/approach This paper presents a review of methodology for MR and describes its early application to judging health effects of alcohol, current uses and a recommended approach of combining MR results with those from observational and experimental studies. Findings Early applications of MR to health effects of alcohol consumption were inadequate for providing unbiased results, but newer attempts using polygenic scores show promise. It is important to combine data from MR analyses with those from observational and experimental studies to obtain an unbiased and scientifically sound estimate of alcohol’s effects on health. Practical implications Giving advice to the public regarding alcohol consumption must be based on accurate, unbiased scientific data; this paper describes attempts to use MR for achieving this goal. Social implications Given that light-to-moderate alcohol intake is associated with a lower risk of CHD, type II diabetes mellitus and total mortality, it is important to be able to evaluate both the benefits and harms from alcohol before giving advice regarding drinking. Originality/value This is part of a group of three papers dealing with the potential health benefits and harms associated with alcohol consumption.

Are there non-linear relationships between alcohol consumption and long-term health?: A systematic review of observational studies employing approaches to improve causal inference

“…As approaches to minimize these biases consist largely of literature-informed, considered researcher decisions and sensitivity analyses, they are not suited to systematic database searching, and were not the focus of this review. While MR is largely immune to both misclassification and confounding, it suffers from its own idiosyncratic limitations, with controversy over its application to alcohol-health research specifically (45)(46)(47). For example, two of the included MR studies discretized genetically-predicted alcohol consumption, resulting in the lowest categories aligning with occasional consumption -not strictly comparable with abstinence.…”

“…Additionally, despite evidence of the importance of accounting for pattern of consumption (48), MR studies are limited in their ability to do so (47), and only one cohort study (31) used drinking pattern as the exposure, rather than volume alone (or volume and frequency separately).…”