Effects of residential greenness and genetic predisposition on hemoglobin A1c and type 2 diabetes: Gene-environment interaction analysis from a nationwide study

Abstract

BackgroundCurrent evidence on the relations of residential greenness with glucose homeostasis and type 2 diabetes (T2D) remained largely uncertain. Most importantly, no prior studies have investigated whether genetic predisposition modifies the above associations. MethodsWe leveraged data from the UK Biobank prospective cohort study, with participants enrolled between 2006 and 2010. Residential greenness was assessed by using the Normalized Difference Vegetation Index, and the weighting T2D-specific genetic risk score (GRS) was constructed based on previously published genome-wide association studies. Linear regression models and logistic regression models were used to investigate associations of residential greenness with glycated hemoglobin (HbA1c) and T2D prevalence, respectively. Interaction models explored whether genetic predisposition modifies greenness-HbA1c/T2D associations. ResultsAmong 315,146 individuals (mean [SD] age, 56.59 [8.09] years), each one-unit increase in residential greenness was associated with reduction in HbA1c (β: −0.87, 95% CI: −1.16 to −0.58) and a 12% decrease in odds of T2D (OR: 0.88, 95% CI: 0.79 to 0.98), respectively. Additionally, interaction analyses further demonstrated that residential greenness and genetic risk had cumulative effects on HbA1c and T2D. Compared with individuals who were exposed to low greenness and had high GRS, participants with low GRS and high greenness had a significant decline in HbA1c (β: −2.96, 95% CI: −3.10 to −2.82, P for interaction = 0.04) and T2D (OR: 0.47, 95% CI: 0.45 to 0.50, P for interaction = 0.09). ConclusionsWe add novel evidence that residential greenness has protective effects on glucose metabolism and T2D, and those beneficial effects can be amplified by low genetic risk. Our findings may facilitate the improvement of the living environment and the development of prevention strategies by considering genetic susceptibility to T2D.