摘要Objective To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease.Methods This prospective cohort study included 318,085 biobank participants from the UK.Physical activity was assessed using the short form of the International Physical Activity Questionnaire.The participants were stratified into low-,intermediate-,and high-genetic-risk groups based on their polygenic risk scores.Multivariate Cox regression models and multiplicative interaction analyses were used.Results During a median follow-up period of 13 years,9,209 participants were diagnosed with chronic obstructive pulmonary disease.For low genetic risk,compared to low physical activity,the hazard ratios(HRs)for moderate and high physical activity were 0.853(95%confidence interval[CI]:0.748-0.972)and 0.831(95%CI:0.727-0.950),respectively.For intermediate genetic risk,the HRs were 0.829(95%CI:0.758-0.905)and 0.835(95%CI:0.764-0.914),respectively.For participants with high genetic risk,the HRs were 0.809(95%CI:0.746-0.877)and 0.818(95%CI:0.754-0.888),respectively.A significant interaction was observed between genetic risk and physical activity.Conclusion Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups,highlighting the need to tailor activity interventions for genetically susceptible individuals.