Objective To screen single-nucleotide polymorphisms (SNPs) loci from previous genome-wide association study (GWAS) related to postpartum type 2 diabetes mellitus (T2DM) among women with previous gestational diabetes mellitus (GDM).
Methods Using the baseline data of a random intervention study on GDM in Tianjin city, we recruited 80 patients and 1 160 non-patients of postpartum T2DM from 1 240 women with GDM history between 2009 and 2010. The blood samples of the participants were collected for SNPs detection of 40 loci related to postpartum T2DM according to prvious GWAS. Based on the variance of T2DM genetic risk explained by each allele, the area under the curve of receiver operating characteristic (ROC), the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI) were used to select targeted SNPs predicting potential high-risk of postpartum T2DM for the women with GDM.
Results Totally 39 models were developed by adding the SNPs loci one by one according to their genetically explained proportion of postpartum T2DM risk (PVi), and all the models included the SNP locus (rs10906115) with the highest estimated PVi. Analyses of the models revealed one SNP locus could significantly improve the AUC (P = 0.019), eight SNP loci could significantly improve the IDI, and eight SNP loci could significantly improve the NRI (P < 0.05 for all). Totally 11 SNP loci (rs10906115, rs2779116, rs7034200, rs7041847, rs780094, rs5015480, rs11212617, rs831571, rs7944584, rs6815464, and rs35767) were identified with potential application in predicting postpartum T2DM among the women with GDM history, which together could explained 5.5% of cumulative genetic risk of postpartum T2DM among the women with GDM history.
Conclusion Among 40 GWAS-identified SNP loci associated with postpartum T2DM among women with GDM history, 11 SNP loci with significant improvement in risk prediction or risk reclassification could be used to predict potential risk of postpartum T2DM after GDM.
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