Genetic and clinic predictors of new onset diabetes mellitus after transplantation

New Onset Diabetes after Transplantation (NODAT) is a frequent complication after solid organ transplantation, with higher incidence during the first year. Several clinical and genetic factors have been described as risk factors of Type 2 Diabetes (T2DM). Additionally, T2DM shares some genetic factors with NODAT. We investigated if three genetic risk scores (w-GRS) and clinical factors were associated with NODAT and how they predicted NODAT development 1 year after transplantation. In both main ( n = 725) and replication ( n = 156) samples the clinical risk score was significantly associated with NODAT (OR main : 1.60 [1.36–1.90], p = 3.72*10 −8 and OR replication : 2.14 [1.39–3.41], p = 0.0008, respectively). Two w-GRS were significantly associated with NODAT in the main sample (OR w-GRS 2 :1.09 [1.04–1.15], p = 0.001 and OR w-GRS 3 :1.14 [1.01–1.29], p = 0.03) and a similar OR w-GRS 2 was found in the replication sample, although it did not reach significance probably due to a power issue. Despite the low OR of w-GRS on NODAT compared to clinical covariates, when integrating w-GRS 2 and w-GRS 3 in the clinical model, the Area under the Receiver Operating Characteristics curve (AUROC), specificity, sensitivity and accuracy were 0.69, 0.71, 0.58 and 0.68, respectively, with significant Likelihood Ratio test discrimination index ( p -value 0.0004), performing better in NODAT discrimination than the clinical model alone. Twenty-five patients needed to be genotyped in order to detect one misclassified case that would have developed NODAT 1 year after transplantation if using only clinical covariates. To our knowledge, this is the first study extensively examining genetic risk scores contributing to NODAT development.