Department of Medicine, McMaster University, Hamilton, Canada; Population Health Research Institute, Hamilton, Canada
Jayneel Limbachia
Population Health Research Institute, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
Karleen M Schulze
Population Health Research Institute, Hamilton, Canada
Dipika Desai
Population Health Research Institute, Hamilton, Canada
Brian Kelly
Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom
Russell J de Souza
Population Health Research Institute, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
Population Health Research Institute, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
Deborah A Lawlor
Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Bristol NIHR Biomedical Research Centre, Bristol, United Kingdom
John Wright
Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom
Department of Medicine, McMaster University, Hamilton, Canada; Population Health Research Institute, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
On behalf of for the Born in Bradford and START investigators
South Asian women are at increased risk of developing gestational diabetes mellitus (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 4372 pregnant South Asian women from the SouTh Asian BiRth CohorT (START) and Born in Bradford (BiB) cohort studies underwent a 75-g glucose tolerance test. PRSs were derived using genome-wide association study results from an independent multi-ethnic study (~18% South Asians). Associations with fasting plasma glucose (FPG); 2 hr 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% confidence interval, 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 alone, and 21.7% when combined with family history. A few weak PRS and GDM risk factors interactions modulating FPG and GDM were observed. Taken together, these results show that a T2D PRS and family history of diabetes are strongly and independently associated with multiple GDM-related traits in women of South Asian descent, an effect that could be modulated by other environmental factors.
