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Assessing the health effects of alcohol consumption, mechanisms of action, and associated disease burden

In plain English

AI plain-English summary

A single genetic variant can make someone unable to tolerate alcohol, and researchers are now using this natural experiment to test whether even moderate drinking causes disease. The problem is that observational studies cannot easily separate the effects of alcohol from the lifestyle factors that often accompany it. People who drink moderately tend to be wealthier and healthier in other ways, making it hard to know whether the drink or the lifestyle explains their lower disease risk. This project uses genetic variants that alter alcohol metabolism as a kind of random assignment, mimicking a clinical trial. It will also analyse blood biomarkers and other molecular data to uncover the biological pathways through which alcohol damages the body. If the research succeeds, it will produce a definitive map of which diseases alcohol actually causes and which it does not. That evidence could reshape global burden-of-disease estimates, which currently rely on weaker observational data, and directly inform national guidelines on safe drinking limits. The work is primarily applied—it aims to produce actionable public health evidence rather than fundamental discovery—but the multi-omics component may also reveal new drug targets for alcohol-related liver and heart disease.

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Alcohol consumption is a major cause of death and disability worldwide. Despite its hazards, alcohol consumption is still widespread and has been increasing in many low- and middle-income countries. Moreover, the associations of alcohol drinking with many diseases and causal nature of the associations, especially moderate drinking, remain uncertain. Furthermore, the underlying mechanisms through which alcohol influences different diseases are still poorly understood. The proposed research aims to investigate comprehensively the causal relevance of alcohol drinking for a phenome-wide range of mental and physical health outcomes and to explore the underlying biological mechanisms. It will utilise genetic, multi-omics and extensive health record data in diverse populations, including the prospective China Kadoorie Biobank and UK Biobank, each of 0.5 million adults. There are four integrated work packages, covering (i) phenome-wide associations of alcohol drinking with disease risks; (ii) genetic epidemiology to assess causality of alcohol-disease associations; (iii) multi-omic approaches to identify novel alcohol-associated biomarkers and disease pathways; and (iv) alcohol- attributable disease burden. The study findings will expand the scope of alcohol-related harms, contribute new evidence to update the estimated global burden and costs of alcohol use, advance prevention and management of alcohol- related diseases, and inform national and global alcohol control policies.

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Researchers

Pek Kei Im (EPMC Awardee)

Related Research

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Original classification

Career Development Award

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