Causal effect of physical activity and sedentary behavior on the risk of alcohol dependence: A bidirectional two-sample Mendelian randomization study

Abstract

BackgroundAlcohol dependence, influenced by physical activity (PA) and sedentary behavior, lacks clear causal clarity. This study aims to clarify causal relationships by estimating these effects using bidirectional two-sample Mendelian randomization (MR). MethodsA bidirectional multivariable two-sample MR framework was employed to assess the causal effects of PA and sedentary behavior on alcohol dependence. Summarized genetic association data were analyzed for four PA-related activity patterns—moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA), accelerometer-based physical activity with average acceleration (AccAve), and accelerometer-based physical activity with accelerations greater than 425 milli-gravities (Acc425)—and three sedentary behavior patterns—sedentary, TV watching, and computer use. The study was expanded to include the examination of the relationship between sedentary behavior or PA and general drinking behavior, quantified as drinks per week (DPW). We obtained summarized data on genetic associations with four PA related activity patterns (MVPA, VPA, AccAve and Acc425) and three sedentary behavior related behavior patterns (sedentary, TV watching and computer use). ResultsMR analysis found AccAve inversely associated with alcohol dependence risk (OR: 0.87; 95% CI: 0.80–0.95; p < 0.001), MVPA positively associated (OR: 2.86; 95%CI: 1.45–5.66; p = 0.002). For sedentary behavior and alcohol dependence, only TV watching was positively associated with the risk of alcohol dependence (OR: 1.43; 95%CI: 1.09–1.88; p = 0.009). No causal links found for other physical or sedentary activities. Reverse analysis and sensitivity tests showed consistent findings without pleiotropy or heterogeneity. Multivariate MR analyses indicated that while MVPA, AccAve and TV watching are independently associated with alcohol dependence, DPW did not show a significant causal relationship. ConclusionsOur results suggest that AccAve is considered a protective factor against alcohol dependence, while MVPA and TV watching are considered risk factors for alcohol dependence. Conversely, alcohol dependence serves as a protective factor against TV watching. Only TV watching and alcohol dependence might mutually have a significant causal effect on each other.