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Topiwala A, Taschler B, Ebmeier KP, Smith S, Zhou H, Levey DF, Codd V, Samani NJ, Gelernter J, Nichols TE, Burgess S. Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol's effects. Molecular Psychiatry. 2022 Oct 1; 27(10):4001-4008.
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) ß? = -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 ß? = -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.