Genetic risk score for risk prediction of diabetic nephropathy in Han Chinese type 2 diabetes patients

We evaluated whether genetic information could offer improvement on risk prediction of diabetic nephropathy (DN) while adding susceptibility variants into a risk prediction model with conventional risk factors in Han Chinese type 2 diabetes patients. A total of 995 (including 246 DN cases) and 519 (including 179 DN cases) type 2 diabetes patients were included in derivation and validation sets, respectively. A genetic risk score (GRS) was constructed with DN susceptibility variants based on findings of our previous genome-wide association study. In derivation set, areas under the receiver operating characteristics (AUROC) curve (95% CI) for model with clinical risk factors only, model with GRS only, and model with clinical risk factors and GRS were 0.75 (0.72-0.78), 0.64 (0.60-0.68), and 0.78 (0.75-0.81), respectively. In external validation sample, AUROC for model combining conventional risk factors and GRS was 0.70 (0.65-0.74). Additionally, the net reclassification improvement was 9.98% (P = 0.001) when the GRS was added to the prediction model of a set of clinical risk factors. This prediction model enabled us to confirm the importance of GRS combined with clinical factors in predicting the risk of DN and enhanced identification of high-risk individuals for appropriate management of DN for intervention.