Functional genetic variants and susceptibility and prediction of gestational diabetes mellitus

The aetiological mechanism of gestational diabetes mellitus (GDM) has still not been fully understood. The aim of this study was to explore the associations between functional genetic variants screened from a genome-wide association study (GWAS) and GDM risk among 554 GDM patients and 641 healthy controls in China. Functional analysis of single nucleotide polymorphisms (SNPs) positively associated with GDM was further performed. Univariate regression and multivariate logistic regression analyses were used to screen clinical risk factors, and a predictive nomogram model was established. After adjusting for age and prepregnancy BMI, rs9283638 was significantly associated with GDM susceptibility (P < 0.05). Moreover, an obvious interaction between rs9283638 and clinical variables was detected (P_interaction < 0.05). Functional analysis confirmed that rs9283638 can regulate not only target gene transcription factor binding, but it also regulates the mRNA levels of SAMD7 (P < 0.05). The nomogram model constructed with the factors of age, FPG, 1hPG, 2hPG, HbA1c, TG and rs9283638 revealed an area under the ROC curve of 0.920 (95% CI 0.902-0.939). Decision curve analysis (DCA) suggested that the model had greater net clinical benefit. Conclusively, genetic variants can alter women's susceptibility to GDM by affecting the transcription of target genes. The predictive nomogram model constructed based on genetic and clinical variables can effectively distinguish individuals with different GDM risk factors.