The Genetic Risk of Gestational Diabetes in South Asian women

ABSTRACT South Asian women are at increased risk of developing gestational diabetes (GDM). Few studies have investigated the genetic contributions to GDM risk. We investigated the association of a type 2 diabetes (T2D) polygenic risk score (PRS), on its own, and with GDM risk factors, on GDM-related traits using data from two birth cohorts in which South Asian women were enrolled during pregnancy. 837 and 4,372 pregnant South Asian women from the SouTh Asian BiRth CohorT (START) and Born in Bradford (BiB) cohort studies underwent a 75-gram glucose tolerance test. PRSs were derived using GWAS results from an independent multi-ethnic study (∼18% South Asians). Associations with fasting plasma glucose (FPG); 2h post-load glucose (2hG); area under the curve glucose; and GDM were tested using linear and logistic regressions. The population attributable fraction (PAF) of the PRS was calculated. Every 1 SD increase in the PRS was associated with a 0.085 mmol/L increase in FPG ([95%CI=0.07-0.10], P=2.85 × 10 −20 ); 0.21 mmol/L increase in 2hG ([95%CI=0.16-0.26], P=5.49 × 10 −16 ); and a 45% increase in the risk of GDM ([95%CI=32-60%], P=2.27 × 10 −14 ), independent of parental history of diabetes and other GDM risk factors. PRS tertile 3 accounted for 12.5% of the population’s GDM. No consistent interactions of the PRS with BMI, or diet quality were observed. A T2D PRS is strongly associated with multiple GDM-related traits in women of South Asian descent, and accounts for a substantial proportion of the PAF of GDM.