A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in telomere length

Abstract

Abstract Background: There is ongoing controversy over the potential for telomere shortening caused by alcohol consumption and smoking. Therefore, the purpose of this study is to investigate the possibility of a relationship between telomere length and alcohol consumption or smoking. Methods: To evaluate the causal relationship of smoking and alcohol consumption on telomere length, we conducted a bidirectional 2-sample Mendelian randomization (MR) analysis. Genetic associations of telomere length (n = 472,174) and lifetime smoking (n = 462,690) were obtained from UK Biobank datasets, and genetic associations of smoking initiation (n = 1,232,091), smoking cessation (n = 547,219), cigarettes per day (n = 337,334), and drinks per week (n = 941,280) were obtained from genome-wide association studies (GWAS) research. We used the inverse-variance weighted (IVW), weighted median, weighted mode, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and MR Egger regression methods to evaluate the association of genetically predicted exposure with the risk of outcome. Results: MR demonstrated the higher risk of shorter telomere length was significantly associated with smoking initiation (β = -0.063, 95% confidence interview (CI): -0.082, -0.045, p < 0.05), smoking cessation (β = -0.1, 95%CI: -0.168, -0.032, p = 0.003), cigarettes per day (β = -0.05, 95%CI: -0.093, -0.007, p = 0.021), lifetime smoking (β = -0.182, 95%CI: -0.244, -0.121, p < 0.05), and drinks per week (β = -0.079, 95%CI: -0.143, -0.014, p = 0.016). But the reversal causality was not found. Conclusion: Our results provide evidence of potential causal association of smoking and alcohol consumption on telomere length. It may contribute to the prevention of premature shortening of telomere length.