Residential green space mitigates genetic susceptibility to incident irritable bowel syndrome in a prospective cohort of 376 749 individuals

Background: Environmental exposures may influence irritable bowel syndrome (IBS) pathogenesis, but the interplay between genetic risk, residential green/blue space, and IBS incidence remains unexplored. Methods: We aimed to study the association between green/blue space and incident IBS, and to assess effect modification by genetic susceptibility. The study included 376 749 UK Biobank participants at baseline. Residential green space was measured using the normalised difference vegetation index (NDVI), and blue space was defined by distance to the nearest water bodies. For time-to-event analyses, we used Cox proportional hazards models, polygenic risk scores (PRS), and mediation analysis to test gene-environment interactions. Results are presented as hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: During a follow-up of 11.73 years, 7091 incident IBS cases were documented. Higher residential green space exposure was associated with reduced risk of incident IBS. Specifically, within a 1000 m buffer, each interquartile range (IQR) increase in NDVI corresponded to a 5% lower IBS risk (HR = 0.95; 95% CI = 0.91-0.98), with consistent effects observed at 800 m and 500 m buffers. Conversely, a greater distance to water bodies was associated with reduced IBS risk. Stratification by PRS revealed a significant interaction: increased green space (1000 m buffer) reduced IBS risk by 8% exclusively among high-genetic-risk individuals (HR = 0.92; 95% CI = 0.88-0.96), whereas no interaction was observed for blue space. Moreover, physical activity mediated the association between green space and IBS. Conclusions: Increased residential green space exposure is associated with reduced IBS incidence, particularly among individuals with high genetic susceptibility. These findings underscore the importance of urban greening as a public health strategy to mitigate IBS risk, highlighting the potential for targeted environmental interventions to offset genetic predispositions.