42 A polygenic risk score associated with gestational diabetes mellitus

Abstract Abstract: Introduction Gestational diabetes mellitus (GDM) is a state of hyperglycemia during pregnancy. GDM can increase risk of birth complications, and subsequent type 2 diabetes mellitus in the mother and offspring. Risk factors such as diet, BMI, and family history have demonstrated strong association with GDM but no clear pathophysiology has been ascertained. Methods A diagnosis of GDM was abstracted from participant medical records. Analysis was conducted on 41 women with and 320 without GDM. Genotypes of 7 genetic variants were available. Additive and dominant genetic models were evaluated by chi-square and multivariate logistic regression methods. A genetic risk score comprised of total risk alleles among the 7 variants was also evaluated. Results Multivariate logistic regression showed significant, independent, positive associations between body-mass index (BMI), age, the posited genetic risk score and GDM. Genetic variant rs1421085 was associated with GDM in multivariate analysis (OR 2.12, 1.08-4.15, p = 0.029. The polygenic risk score showed association with GDM, odds ratio 1.27, 95% CI 1.09 - 1.48, p = 0.003. Discussion This relatively small cohort replicated a previously proposed polygenic risk score, as well as established risk factors for GDM (age and BMI). A previous meta-analysis in the literature reported a degree of heterogeneity between the 3 large cohorts analyzed, suggesting that the effect of these variants may differ according to genetic background. Conclusion We validate a previously published polygenic risk score for GDM in an ethically unrelated population. (Supported by NIGMS P20GM103442)