Associations between blue space exposure and rheumatoid arthritis: The modifying effect of genetic susceptibility and air pollutants

Studies on the interaction among genetic susceptibility, blue space exposure, and rheumatoid arthritis (RA) risk have been lacking. Therefore, we examined the association between blue space exposure and RA incidence and assess the modifying effect of genetic susceptibility and air pollutants. Form the UK Biobank, 322,783 participants without RA were enrolled in this study. The association between blue space exposure and RA incidence was estimated using a cox proportional hazards model. The combined effect of blue space and genetic factors on the risk of RA was further evaluated. The polygenic risk score (PRS) for RA was calculated to represent individual genetic risk, and the potential modification effect of air pollution on the relationship between blue space, PRS, and RA were explored. During a median follow-up of 12.4 years, 3659 RA cases were identified. A 10 % increase in blue space_{300 m} was associated with a 22.6 % reduction in RA incidence (HR=0.774, 95 % CI: 0.670, 0.895), exhibiting a consistent downward trend in the exposure-response curve. A high PRS was an independent risk factor for RA (HR=1.393, 95 % CI: 1.347, 1.439). The associations between blue space exposure, PRS, and the risk of RA were dose-dependent, with the lowest risk observed among those with high levels of blue space and lower PRS (HR_{bluespace300m}=0.501, 95 % CI: 0.431, 0.583; HR_{bluespace1000m}=0.476, 95 % CI: 0.408, 0.555). Interaction analysis indicated that increased concentrations of air pollutants strengthened the relationship between PRS and RA. Blue space exposure mitigated the risk of RA development, particularly in individuals with low genetic risk.