Associations between alcohol use and accelerated biological ageing

Abstract Background Harmful alcohol use is a leading cause of premature death, and is associated with age-related disease. Ageing is highly variable between individuals, and may deviate from chronological ageing, suggesting that biomarkers of biological ageing (based on DNA methylation or brain structural measures) may be clinically relevant. Here, we investigated the relationships between alcohol phenotypes and both brain and DNA methylation age estimates. Methods First, using data from UK Biobank and Generation Scotland, we tested the association between alcohol consumption (units/week) or hazardous use (AUDIT scores), and accelerated brain and epigenetic ageing in 20,258 and 8,051 individuals, respectively. Second, we used Mendelian randomization to test for a causal effect of alcohol consumption levels and alcohol use disorder (AUD) on biological ageing. Results Alcohol use showed a consistent positive association with higher predicted brain age (AUDIT-C: β=0.053, p=3.16×10 −13 ; AUDIT-P: β=0.052, p=1.6×10 −13 ; total AUDIT score: β=0.062, p=5.52×10 −16 ; units/week: β=0.078, p=2.20×10 −16 ), and DNA methylation GrimAge (Units/week: β=0.053, p=1.48×10 − 7 ) and PhenoAge (Units/week: β=0.077, p=2.18×10 −10 ). Mendelian randomization analyses revealed some evidence for a causal effect of AUD on accelerated brain ageing (β=0.272, p=0.044), and no evidence for a causal effect of alcohol consumption levels on accelerated biological ageing. Conclusions We provide consistent phenotypic evidence linking alcohol use with accelerated biological ageing. There is possible evidence for a causal effect of AUD on brain age, but not for any other alcohol-related trait on brain or epigenetic age acceleration. Future studies investigating the mechanisms associating alcohol use with accelerated biological ageing are warranted.