Abstract
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 modu-lating 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.
| Original language | English |
|---|---|
| Article number | e81498 |
| Journal | eLife |
| Volume | 11 |
| Early online date | 22 Nov 2022 |
| DOIs | |
| Publication status | Published - 23 Nov 2022 |
Bibliographical note
Funding Information:Research projects in START and Born in Bradford are only possible because of the enthusiasm and commitment of the parents and children involved in these two studies. The authors are grateful to all the participants, teachers, school staff, health professionals, and researchers, and other contributors who have made these studies happen. Studies: The South Asian Birth Cohort (START) study data were collected as part of a program funded by the Indian Council of Medical Research in Canada and by the Canadian Institutes of Health Research (Grant INC-109205), and the Heart and Stroke Foundation (Grant NA7283) with founding principal investigators: Sonia S Anand, Anil Vasudevan, Milan Gupta, Katherine Morrison, Anura Kurpad, Koon K Teo, and Krishnamachari Srinivasan. The Born in Bradford (BiB) The Born in Bradford cohort is funded by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044). The study also receives funding from the Wellcome Trust (WT101597MA), a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1) and the British Heart Foundation (CS/16/4/32482). DNA extraction was funded by the UK Medical Research Council via the Integrative Epidemiology Unit (MRC IEU; MC_UU_12013/5) and genotyping via the MRC IEU and a National Institute of Health Research Senior Investigator Award to DAL (NF-0616-10102). Research associate (AL) and graduate student (JL) costs were covered by two Canadian Institutes of Health Research Grants [Project grant number: 298104, Foundation Scheme grant number: FDN-143255, Study grant numbers: INC 109205, NA 7283] awarded to SSA; DAL’s contribution to this study is supported by the Bristol NIHR Biomedical Research Centre, the UK Medical Research Council (MC_ UU_00011/6) and the British Heart Foundation (CH/F/20/90003). SSA is supported by a Tier 1 Canada Research Chain in Ethnic Diversity and Cardiovascular Disease, and a Heart and Stroke Foundation/ Michael G DeGroote Chair in Population Health Research at McMaster University.
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