Association of Rest-Activity Rhythm With the Risk of Rheumatoid Arthritis and Effect Modification by Genetic Susceptibility

Objective To investigate the association between rest-activity rhythm (RAR) and the risks of rheumatoid arthritis (RA), and to evaluate whether genetic susceptibility modifies this relationship.

Methods This prospective cohort study utilized data from the UK Biobank, including 88060 participants who did not have RA at baseline. RAR parameters (e.g., relative amplitude) were calculated using data obtained through wrist-worn accelerometers. The participants’ genetic susceptibility to RA was assessed using a polygenic risk score. Cox proportional hazards models were employed to analyze the association between RAR and RA risk, with interaction terms incorporated to evaluate the effect modification by genetic susceptibility.

Results Over a median follow-up period of 7.97 years, 660 incident RA cases were identified. After adjusting for age, sex, ethnicity, educational attainment, Townsend deprivation index, drinking status, smoking status, dietary score, body mass index, and polygenic risk score for incident RA, the dose-response analysis revealed a linear relationship between the RAR-related parameters, including the average amplitude during the most active 10 h (M10), interdaily stability (IS), intradaily variability (IV), and the risk of developing RA (P > 0.05). In contrast, relative amplitude and the average amplitude during the least active 5 h (L5) showed a nonlinear relationship with the risk of developing RA (P < 0.05). Compared to those in the the highest quartile of relative amplitude, participants in the lowest quartile had a 49% increase in the risk of developing RA (hazard ratio HR = 1.49; 95% CI, 1.17-1.90). Compared to those in the lowest quartile, participants in the highest quartile of L5 had a 40% increased risk of developing RA (HR = 1.40; 95% CI, 1.12-1.75). Every time M10 increased by one standard deviation, the risk of developing RA decreased by 12% (HR = 0.88; 95% CI, 0.80-0.96). No evidence of effect modification by genetic susceptibility was observed in the RAR-RA association (P > 0.05).

Conclusion Disrupted rest-activity rhythm is associated with an increased risk of RA, which is independent of genetic susceptibility to RA. Our findings suggest that improving rest-activity rhythm may help reduce RA risks.