Joint effects of residential greenness and genetic susceptibility on type 2 diabetes: a prospective cohort study...

Residential greenness has been linked to a reduced risk of type 2 diabetes (T2D), yet whether genetic susceptibility modifies this association remains unclear. Evidence on gene-environment interaction is limited, mainly cross-sectional, and largely from European-ancestry populations. Prospective data from Chinese populations examining the association between residential greenness and incident T2D, as well as glycemic traits, are scarce. In this study, we included 7861 middle-aged and older Chinese adults (aged ≥ 40 years), and assessed residential greenness using the Normalized Difference Vegetation Index (NDVI) derived from Moderate-Resolution Imaging Spectroradiometer (MODIS) satellite imagery, linking it to T2D incidence over a median follow-up of 3.8 years. Genetic susceptibility was assessed in 5389 participants with DNA data using a T2D-specific weighted genetic risk score based on 89 genome-wide significant single-nucleotide polymorphisms identified in East Asian populations, weighted by published effect estimates. Our results show that higher residential greenness was associated with a 44% reduction in T2D risk (hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.48-0.66), as well as improved insulin sensitivity and β-cell function. Notably, genetic susceptibility significantly modified the association between residential greenness and T2D on both multiplicative (P for interaction = 0.019) and additive scales (relative excess risk due to interaction [RERI] = 0.19), with higher greenness conferring greater relative and absolute risk reductions among individuals at medium and high genetic risk. These findings underscore a protective role of residential greenness against T2D, with stronger effects in those at higher genetic risk, supporting environmental interventions to mitigate genetic predisposition in the prevention of T2D.