Alcohol consumption and brain health (360G-Wellcome-216462_Z_19_Z)

Exposure to alcohol is widespread but potentially modifiable. Whilst heavy drinking is recognized as detrimental to the brain, the impact of more moderate intake remains unclear. This project seeks to better understand the relationship between alcohol intake and brain health. Specific aims: \- Examine the causal relationship between alcohol intake and dementia. \- Investigate the causal association between drinking and brain imaging markers. \- Identify mediating pathways between alcohol and brain health. The proposed studies will triangulate large-scale electronic health records with neuroimaging and genetic data in UK Biobank (n=500,000) and Million Veterans Program in the US (n=760,000). The project will include complementary observational and pseudo-experimental (Mendelian randomization) approaches, and examine for consistency of findings across methods. Outcomes: This work will comprise the largest and most in depth study of alcohol’s association with brain health. It has extensive application for the study of other exposures relating to psychiatric phenotypes. The findings are likely to be of widespread interest and relevance to scientific and clinical fields, as well as policy-makers and the public.