Aims/hypothesis: The recent advent of genome-wide association studies has considerably accelerated the identification of type 2 diabetes loci. We aimed to investigate the combined effects of multiple genetic variants, alone or in combination with conventional risk factors, on type 2 diabetes and diabetes-related traits in Han Chinese.
Methods: We genotyped 17 variants in 17 loci in a population-based Han Chinese cohort including 3,210 unrelated individuals. A genetic risk score (GRS) was calculated on the basis of these variants. The discriminatory ability was assessed by the area under the receiver operating characteristics curve.
Results: The odds ratio for type 2 diabetes and hyperglycaemia with each GRS point (per risk allele) was 1.18 (95% CI 1.12-1.23, p = 1.3 x 10(-12)) and 1.12 (95% CI 1.09-1.16, p = 7.5 x 10(-14)), respectively. Compared with participants with GRS < or =11.0 (7.63%), those with GRS > or =19.0 (8.87%) had a 4.58-fold higher risk (95% CI 2.49-8.42) of type 2 diabetes. The GRS also showed a significant association with lower beta cell function estimated by HOMA of beta cell function (p = 8.4 x 10(-10)). In addition, we observed significant interactive effects between GRS and BMI on fasting glucose and HbA(1c) levels (p = 0.04 and p = 0.03 for interaction, respectively). Discrimination of diabetes risk was improved (p < 0.001) when the GRS was added to a model including clinical risk factors. The AUCs were 0.62 and 0.77, respectively, for the GRS and conventional clinic risk factors alone, and 0.79 when the GRS was added.
Conclusions/interpretation: In this Han Chinese population, the GRS of 17 combined variants modestly but significantly improved discrimination of the conventional risk factors for type 2 diabetes.