A Mendelian randomization study on causal effects of leisure sedentary behaviour on the risk of rheumatoid arthritis.

BACKGROUND:The causal inference between leisure sedentary behaviour (LSB) and rheumatoid arthritis (RA) is still controversial because of potential residual confounding and reverse causality. METHODS:The present study used publicly available large-scale genome-wide association studies (GWAS) of LSB (television watching, computer use, and driving) and RA to perform a two-sample Mendelian randomization (MR) study to evaluate the causal effect of LSB on the risk of RA. We detected significant causal associations using the multiplicative random effects-inverse variance weighted (MRE-IVW) method, the maximum likelihood, robust adjusted profile scores, the weighted median, MR-Egger regression, and several complementary sensitivity analyses. Risk factor analysis was also conducted to further investigate potential mediators linking causal inference. RESULTS:Increased genetic liability to leisure television watching was significantly associated with a higher risk of RA (MRE-IVW method; OR = 2.46, 95% CI 1.77-3.41; p = 8.35 × 10-8 ). MR estimates indicated that prolonged leisure computer use was causally associated with a lower risk of RA (MRE-IVW method; OR = 0.23, 95% CI 0.12-0.46; p = 2.19 × 10-5 ). However, we found no evidence for a causal effect of leisure driving on the risk of RA (MRE-IVW method; OR = 0.59, 95% CI 0.10-3.41; p = 0.557). No pleiotropy was detected by the sensitivity analysis. CONCLUSIONS:This study supports a causal association between prolonged leisure television watching and an increased risk of RA. Additionally, prolonged computer use might be a protective factor for RA.