Shared exposure liability of type 2 diabetes and other chronic conditions in the UK Biobank

To investigate whether the cumulative exposure risks of incident T2D are shared with other common chronic diseases.

We first establish and report the cross-sectional prevalence, cross-sectional co-prevalence, and incidence of seven T2D-associated chronic diseases [hypertension, atrial fibrillation, coronary artery disease, obesity, chronic obstructive pulmonary disease (COPD), and chronic kidney and liver diseases] in the UK Biobank. We use published weights of genetic variants and exposure variables to derive the T2D polygenic (PGS) and polyexposure (PXS) risk scores and test their associations to incident diseases.

PXS was associated with higher levels of clinical risk factors including BMI, systolic blood pressure, blood glucose, triglycerides, and HbA1c in individuals without overt or diagnosed T2D. In addition to predicting incident T2D, PXS and PGS were significantly and positively associated with the incidence of all 7 other chronic diseases. There were 4% and 8% of individuals in the bottom deciles of PXS and PGS, respectively, who were prediabetic at baseline but had low risks of T2D and other chronic diseases. Compared to the remaining population, individuals in the top deciles of PGS and PXS had particularly high risks of developing chronic diseases. For instance, the hazard ratio of COPD and obesity for individuals in the top T2D PXS deciles was 2.82 (95% CI 2.39-3.35, P = 4.00 × 10^-33) and 2.54 (95% CI 2.24-2.87, P = 9.86 × 10^-50), respectively, compared to the remaining population. We also found that PXS and PGS were both significantly (P < 0.0001) and positively associated with the total number of incident diseases.

T2D shares polyexposure risks with other common chronic diseases. Individuals with an elevated genetic and non-genetic risk of T2D also have high risks of cardiovascular, liver, lung, and kidney diseases.