孟德尔随机化
端粒
全基因组关联研究
置信区间
饮酒量
观察研究
遗传学
医学
酒
内科学
生物
单核苷酸多态性
基因型
基因
遗传变异
生物化学
作者
Anya Topiwala,Bernd Taschler,Klaus P. Ebmeier,Stephen M. Smith,Hang Zhou,Daniel F. Levey,Veryan Codd,Nilesh J. Samani,Joel Gelernter,Thomas E. Nichols,Stephen Burgess
标识
DOI:10.1038/s41380-022-01690-9
摘要
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.
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