Physical activity and the risk of developing 8 age-related diseases: epidemiological and Mendelian randomization studies

Abstract

We aimed to characterize the associations between physical activity levels and the risk of developing age-related diseases in the Coronary Artery Risk Development in Young Adults (CARDIA) study and used Mendelian randomization (MR) to assess whether there are causal relationships between physical activity levels and the risk of developing 8 age-related diseases (coronary atherosclerosis, ischemic heart disease, angina, Alzheimer’s disease, hypertension, type 2 diabetes, hyperlipidemia, and venous thromboembolism). Based on the data available in the CARDIA, we obtained data related to five disease states: coronary heart disease, hypertension, diabetes, hyperlipidemia, and venous thromboembolism. Binary logistic regression analysis estimated the multivariable-adjusted associations between different physical activity statuses and diseases. For the MR study, we used summary-level data from a recently published genome-wide association study on physical activity (including vigorous physical activity and accelerometer-based physical activity) conducted with participants from the UK Biobank study. We selected the above 8 age-related diseases as our outcomes. In the CARDIA-based analysis, the risk of developing coronary heart disease [OR (95% CI): 0.562 (0.397–0.795)], hypertension [OR (95% CI): 0.703 (0.601–0.821)], diabetes [OR (95% CI): 0.783 (0.620–0.988)], and hyperlipidemia [OR (95% CI): 0.792 (0.662–0.949)] was negatively related to physical activity status when participants achieved the physical activity target. Our MR results support a negative causal association between genetically determined vigorous physical activity levels and the risk of developing 3 age-related diseases, namely, angina, hypertension and type 2 diabetes. Moreover, our results also support a negative causal association between genetically determined accelerometer-based physical activity levels and the risk of developing angina. Promotion of physical activity is likely to prevent specific age-related diseases. 1. When the amount of physical activity reaches the guidelines, coronary heart disease, hypertension, diabetes, and hyperlipidemia are negatively related to physical activity. 2.Our mendelian randomization results support negative causality between genetically determined vigorous physical activity and 3 age-related diseases, including angina, hypertension, and type 2 diabetes. 3. Our results also support negative causality between genetically determined accelerometer-based physical activity and angina.