Associations between alcohol use and accelerated biological ageing

老化 酒精使用障碍鉴定试验 医学 饮酒量 DNA甲基化 酒精使用障碍 内科学 生物 遗传学 基因 生物化学 基因表达
作者
Sunniva M. K. Bøstrand,Kadi Vaher,Laura de Nooij,Matthew A. Harris,James H. Cole,Simon R. Cox,Riccardo E. Marioni,Daniel L. McCartney,Rosie M. Walker,Andrew M. McIntosh,Kathryn Evans,Heather C. Whalley,Robyn E Wootton,Toni‐Kim Clarke
出处
期刊:Addiction Biology [Wiley]
卷期号:27 (1) 被引量:19
标识
DOI:10.1111/adb.13100
摘要

Harmful alcohol use is a leading cause of premature death and is associated with age-related disease. Biological ageing is highly variable between individuals and may deviate from chronological ageing, suggesting that biomarkers of biological ageing (derived from 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. First, using data from UK Biobank and Generation Scotland, we tested the association between alcohol consumption (units/week) or hazardous use (Alcohol Use Disorders Identification Test [AUDIT] scores) and accelerated brain and epigenetic ageing in 20,258 and 8051 individuals, respectively. Second, we used Mendelian randomisation (MR) to test for a causal effect of alcohol consumption levels and alcohol use disorder (AUD) on biological ageing. 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 two DNA methylation-based estimates of ageing, GrimAge (units/week: β = 0.053, p = 1.48 × 10-7 ) and PhenoAge (units/week: β = 0.077, p = 2.18x10-10 ). MR analyses revealed limited evidence for a causal effect of AUD on accelerated brain ageing (β = 0.118, p = 0.044). However, this result should be interpreted cautiously as the significant effect was driven by a single genetic variant. We found no evidence for a causal effect of alcohol consumption levels on accelerated biological ageing. Future studies investigating the mechanisms associating alcohol use with accelerated biological ageing are warranted.
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