THE IMPACT OF MATERNAL AND/OR NEWBORN GENETIC RISK SCORES ON MATERNAL AND NEWBORN DYSGLYCEMIA

Abstract

Background: South Asians are at an increased risk of developing dysglycemia during and after pregnancy. In pregnant women, dysglycemia often develops in the form of gestational diabetes mellitus (GDM), which may predispose their newborns to adverse health outcomes through abnormal cord blood insulin levels. However, reasons for the elevated risk of dysglycemia in South Asians have not been extensively studied. Genetic factors may contribute to the heritability of GDM and abnormal cord blood insulin levels in South Asians.

Objectives: The objectives of this thesis were to test the association of: 1) A type 2 diabetes polygenic risk score with GDM in South Asian pregnant women from the South Asian Birth Cohort (START); 2) maternal and newborn insulin-based polygenic risk scores with cord blood insulin and glucose/insulin ratio in South Asian newborns from START

Methods: Three polygenic risk scores were created to test their association with participant data (N=1012) from START. GDM was defined using cut-offs established by the Born in Bradford cohort of South Asian women. The type 2 diabetes polygenic risk score was created in 832 START mothers and included 35,274 independent variants. The maternal and newborn insulin-based polygenic risk scores were created in 604 START newborns and included 1128017 independent variants. Univariate and multiple logistic and linear regression models were used to test the associations between the polygenic risk scores and dysglycemia outcomes.

Results: The type 2 diabetes polygenic risk score was associated with GDM in both univariate (OR: 2.00, 95% CI: 1.46-2.75, P<0.001), and multivariable models (OR: 1.81, 95% CI: 1.30-2.53, P<0.001). The maternal insulin-based polygenic risk score was not associated with cord blood insulin or cord glucose/insulin ratio. However, the newborn insulin-based polygenic risk score was associated with cord blood insulin in a multivariable model adjusted for maternal insulin-based polygenic risk score (β = 0.036, 95% CI: 0.002 – 0.069; P=0.038 among other factors.

Conclusion: A type 2 diabetes polygenic risk score and a newborn insulin-based polygenic risk score may be associated with maternal and newborn dysglycemia.