Assessing the health effects of alcohol consumption, mechanisms of action, and associated disease burden (360G-Wellcome-302990_Z_23_Z)

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.