Genome-wide polygenic risk score, cardiometabolic risk factors, and type 2 diabetes mellitus in the Chinese population.
Huang N., Xiao W., Lv J., Yu C., Guo Y., Pei P., Yang L., Millwood IY., Walters RG., Chen Y., Du H., Avery D., Ou T., Chen J., Chen Z., Huang T., Li L., China Kadoorie Biobank Collaborative Group* None.
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