Genome-wide polygenic risk score, cardiometabolic risk factors, and type 2 diabetes mellitus in the Chinese population

Abstract

Objective: Type 2 diabetes (T2D) is caused by both genetic and cardiometabolic risk factors. However, the magnitude of the genetic predisposition of T2D in the Chinese population remains largely unknown.

Methods: This study included 93,488 participants from the China Kadoorie Biobank, and multiple polygenic risk scores (PRS) were calculated. A common cardiometabolic risk score (CRS) using smoking, alcohol consumption, physical activity, diet, obesity, blood pressure, and blood lipids was constructed to investigate the effects of cardiometabolic risk factors on T2D. Furthermore, an equation based on ideal PRS, CRS, and their interaction was established to explore the combined effects on T2D.

Results: An ideally fitting PRS model (variance explained, R² = 7.6%) was reached based on multiple PRS calculation methods. An additive interaction between PRS and CRS (coefficient = 28%, 95% CI: 0.20-0.36, p < 0.001) was found. The R² of the T2D predictive model could increase to 8.3% when CRS and the interaction terms of PRS × CRS were considered. In the etiological composition of T2D, the ratio of genetic risk effect, cardiometabolic risk effect, and interaction between genetic and cardiometabolic factors was 67:16:17.

Conclusions: This study identified an ideally fitting PRS model for identifying and predicting the risk of T2D suitable for the Chinese population. The quantified proportional structure of genetic risk factors, cardiometabolic risk factors, and their interaction was detected, which elucidated the critical effect of genetic factors.