Abstract
OBJECTIVE: Observational studies have found that cigarette smoking increased the prevalence and incidence of sarcopenia, whereas alcohol consumption appeared to decrease the risk. These findings, however, may be susceptible to either confounding bias or reverse causation. We conducted a Mendelian randomisation (MR) study to appraise the causal relation of cigarette smoking and alcohol consumption to the risk of sarcopenia. METHODS: Genetic instruments associated with cigarette smoking (cigarettes per day) and alcohol consumption (drinks per week) were retrieved from the publicly available genome-wide association data. Individual-level, electronic medical record-linked data on sarcopenia, grip strength and appendicular lean mass were obtained from the UK Biobank. We performed two-sample univariable and multivariable MR analyses to examine the relation of genetically determined cigarette smoking and alcohol consumption to the risk of sarcopenia and its indices. RESULTS: One SD increase of genetically determined cigarette smoking was associated with an increased risk of sarcopenia (OR=2.51, 95% CI: 1.26 to 5.01, p=0.001), decreased grip strength (β=-0.63 kg, 95% CI: -1.13 to -0.13, p=0.01) and less appendicular lean mass (β=-0.22 kg, 95% CI: -0.44 to -0.01, p=0.04). Although one SD increase of genetically determined alcohol consumption was associated with decreased grip strength (β=-1.15 kg, 95% CI: -2.09 to -0.10, p=0.02), no statistically significant causal association was observed between genetically determined alcohol consumption and either sarcopenia (OR=0.96, 95% CI: 0.35 to 2.62, p=0.94) or appendicular lean mass (β=-0.23 kg, 95% CI: -0.91 to 0.45, p=0.51). CONCLUSIONS: Our findings showed that genetically determined cigarette smoking, but not alcohol consumption, was causally associated with the risk of sarcopenia.