IMPORTANCEThe risk of airflow limitation and chronic obstructive pulmonary disease (COPD) is influenced by combinations of cigarette smoking and genetic susceptibility, yet it remains unclear whether gene-by-smoking interactions are associated with quantitative measures of lung function. OBJECTIVE To assess the interaction of cigarette smoking and polygenic risk score in association with reduced lung function. DESIGN, SETTING, AND PARTICIPANTS This UK Biobank cohort study included UK citizens of European ancestry aged 40 to 69 years with genetic and spirometry data passing quality control metrics. Data was analyzed from July 2020 to March 2021.EXPOSURES PRS of combined forced expiratory volume in 1 second (FEV 1 ) and percent of forced vital capacity exhaled in the first second (FEV1/FVC), self-reported pack-years of smoking, ever-vs never-smoking status, and current-vs former-or never-smoking status.MAIN OUTCOMES AND MEASURES FEV 1 /FVC was the primary outcome. Models were used to test for interactions with models, including the main effects of PRS, different smoking variables, and their cross-product terms. The association between pack-years of smoking and FEV 1 /FVC were compared for those in the highest vs lowest decile of estimated genetic risk for low lung function.
RESULTSWe included 319 730 individuals, of whom 24 915 (8%) had moderate-to-severe COPD cases, and 44.4% were men. Participants had a mean (SD) age 56.5 of (8.02