Alcohol’s impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption (n = 941,280) and alcohol use disorder (AUD) (n = 57,564 cases). Non-linear MR employed UK Biobank individual data. MR analyses suggested a causal relationship between alcohol traits, more strongly for AUD, and telomere length. Higher genetically-predicted AUD (inverse variance-weighted (IVW) β = −0.06, 95% confidence interval (CI): −0.10 to −0.02, p = 0.001) was associated with shorter telomere length. There was a weaker association with genetically-predicted alcoholic drinks weekly (IVW β = −0.07, CI: −0.14 to −0.01, p = 0.03). Results were consistent across methods and independent from smoking. Non-linear analyses indicated a potential threshold relationship between alcohol and telomere length. Our findings indicate that alcohol consumption may shorten telomere length. There are implications for age-related diseases.

酒精对端粒长度（生物衰老的一个拟议标志）的影响尚不清楚。我们进行了迄今为止最大规模的观察性研究（ n = 245,354 名英国生物银行参与者），并将研究结果与孟德尔随机化 (MR) 估计值进行了比较。两个样本 MR 使用了最近一项端粒长度全基因组关联研究 (GWAS) 中 472,174 名参与者的数据。根据与饮酒（ n = 941,280）和酒精使用障碍（AUD）（ n = 57,564 例）的关联来选择遗传变异。非线性MR采用英国生物银行个体数据。 MR 分析表明，酒精特征（对于 AUD 而言更为强烈）与端粒长度之间存在因果关系。较高的遗传预测 AUD（逆方差加权 (IVW) β = -0.06，95% 置信区间 (CI)：-0.10 至 -0.02， p = 0.001）与较短的端粒长度相关。与基因预测的每周饮酒量的相关性较弱（IVW β = -0.07，CI：-0.14 至 -0.01， p = 0.03）。不同方法的结果是一致的，并且与吸烟无关。非线性分析表明酒精和端粒长度之间存在潜在的阈值关系。我们的研究结果表明，饮酒可能会缩短端粒长度。这对与年龄相关的疾病有影响。