Total sitting time and COPD in NHANES, with genetic evidence for leisure television watching: A cross-sectional and...

Observational total sitting time and genetically proxied leisure television watching are related but non-identical sedentary phenotypes. We examined their complementary associations with chronic obstructive pulmonary disease (COPD) and explored smoking and C-reactive protein as potential mediators of the genetic association. We analyzed adults aged 40 years or older in the National Health and Nutrition Examination Survey 2013-2018 using survey-weighted logistic regression. Total sitting time was evaluated at 480 minutes/day, continuously per 60 minutes/day, and in 5 categories. Sensitivity analyses used a more specific COPD definition requiring self-reported physician-diagnosed COPD plus current respiratory prescription medication. Complementary two-sample Mendelian randomization (MR), two-step MR mediation, and multivariable MR analyses evaluated leisure television watching, leisure computer use, and driving. Among 11,343 participants, 655 reported physician-diagnosed COPD. Sitting for at least 480 minutes/day was associated with prevalent COPD after multivariable adjustment (OR, 1.34; 95% confidence interval (CI), 1.03-1.74). Each additional 60 minutes/day was associated with an OR of 1.06 (95% CI, 1.01-1.12), and the OR for at least 600 versus <240 minutes/day was 1.78 (95% CI, 1.06-3.01; P for trend = .032). Findings persisted after additional physical-activity adjustment and with the more specific COPD definition. Genetically predicted LTW was associated with COPD (random-effects inverse-variance weighted OR per 1-standard deviation increment, approximately 1.5 hour/day, 1.96; 95% CI, 1.66-2.30; P = 5.27 × 10-16), with moderate heterogeneity (I2 = 35.9%). Two-step MR suggested approximate mediated proportions of 28.0% for smoking and 5.8% for C-reactive protein. Greater total sitting time was cross-sectionally associated with prevalent self-reported COPD, while genetically proxied LTW showed a complementary association with COPD risk. The observational finding remains vulnerable to reverse causation and misclassification, and the mediation and multivariable MR findings should be regarded as supportive and approximate rather than definitive because of heterogeneity, possible pleiotropy, and unquantified conditional instrument strength.