Soft water exposure increases the effect of genetic susceptibility on the risk of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is influenced by both genetic and environmental factors. The mineral content of domestic water plays an essential role in human health. However, the relationship between water mineral content, genetic predisposition, and RA risk remains unclear.

Methods: This observational study included 434,958 individuals to investigate the association between mineral content in domestic water, genetic risk, and the incidence of RA. The cohort comprised RA-free participants with complete data on water mineral levels, genetic profiles, lifestyle factors, and physical measurements at baseline. A polygenic risk score (PRS) for RA was calculated for each participant to assess genetic susceptibility. Cox regression models were used to examine associations between water mineral concentrations, PRS, and RA risk. Stratified analyses were performed to evaluate the modifying effect of water mineral content on genetic risk.

Results: During a median follow-up of 15 years, 5880 new RA cases were recorded. After adjusting for multiple covariates, higher concentrations of calcium carbonate in domestic water were associated with a reduced risk of RA (hazard ratio [HR] = 0.93; 95 % confidence interval [CI]: 0.90 to 0.95; p = 1.74 × 10). Individuals in the highest PRS tertile had a 53 % to 74 % increased risk of RA compared to those in the lowest tertile. Notably, those with both the highest PRS and exposure to soft water had a 92 % (95 % CI: 71 % to 115 %) increased risk of RA compared to individuals with the lowest PRS and exposure to very hard water. Multiple sensitivity analyses confirmed the robustness of these findings.

Conclusions: These results suggest that exposure to hard water may reduce the risk of RA, particularly in individuals with high genetic susceptibility.