Polyexposure score for T2D Genome-Wide Association Summary Statistics

While genotypes, behavior, and environmental exposures form a complex web of interrelated associations in type 2 diabetes (T2D), their interaction is poorly understood. In the following, we identify genetic determinants of a “polyexposure risk score” (PXS), a risk score that summarizes environmental and behavioral risk factors that predict longitudinal T2D incidence consisting of 25 associated individual-level behaviors in the UK Biobank. PXS-T2D had a non-zero heritability (h2 = 0.18), and we find extensive shared genetic architecture with established clinical and biological determinants of T2D, most prominently with body mass index (genetic correlation [rg] = 0.57) and Homeostatic Model Assessment for Insulin Resistance (rg = 0.51). Genes associated with PXS-T2D were enriched for expression in the brain. Leveraging biobank scale data with genetic information can inform how exposure and behavior impact T2D across axes of diabetes risk. Enclosed are PXS-T2D GWAS summary statistics (both unadjusted and adjusted by body mass index).