Joint Effects of Calcium Carbonate in Domestic Water and the Genetic Risk on Rheumatoid Arthritis

Background : The aim of this study was to investigate the relationship between minerals in domestic water and the incidence of rheumatoid arthritis (RA). Methods : This longitudinal observational study included 434,958 British individuals from the United Kingdom. The study population consisted of RA-free participants with complete information on water minerals, genetic data, lifestyle habits, and physical measurements at baseline. The baseline assessment was conducted between 2006 and 2010, and the follow-up period was up to 2024. To assess individual genetic susceptibility, a polygenic risk score (PRS) of RA was calculated for each participant. Cox regression models were employed to examine the associations between water minerals, the PRS, and the occurrence of RA. Results : A total of 5,880 new RA cases were reported during a median follow-up of 15 years. After controlling for multiple covariates, the concentration of calcium carbonate in domestic water was negatively associated with the risk of RA (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.90 to 0.95; p=1.74×10 ^-9 ). Additionally, individuals in the highest tertile of the polygenic risk score (PRS) had a 53% to 74% increased risk of RA compared with those in the lowest tertile. Notably, individuals with a high PRS and soft water had a 92% (95% CI: 71% to 115%) increased risk of RA compared with those with a low PRS and very hard water. Conclusions : The results suggest that exposure to soft water increases the risk of RA, especially in people who are genetically susceptible.