Associations between alcohol use and accelerated biological ageing

Abstract

BackgroundHarmful 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.MethodsFirst, 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.ResultsAlcohol 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.ConclusionsWe 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.

Association between the Epigenetic Lifespan Predictor GrimAge and History of Suicide Attempt in Bipolar Disorder

“…We explored whether the relationship between SA and GrimAgeAccel was attenuated when covarying for these indexes of severity (Tables 4 and S5) and found that substance abuse may account for some of the higher GrimAgeAccel observed with SA. Previous studies have documented the association between substance abuse and accelerated aging [58,59].…”

Commentary on Whitsel et al.: Smoking, alcohol use and the brain‐ the challenge of answering causal questions

“…Their findings provide evidence that smoking causally increases the occurrence of white matter hyperintensities, suggesting that smoking accelerates brain ageing (alcohol was not studied). Another MR study investigated effects of alcohol consumption and hazardous alcohol use on a composite measure of predicted brain age [4]. They found consistent evidence that higher alcohol consumption causally increases brain age, and limited evidence that alcohol use disorder has similar effects (with the cautionary note that the latter was largely driven by a single genetic variant).…”