The genetic risk of gestational diabetes in South Asian women

  1. Amel Lamri
  2. Jayneel Limbachia
  3. Karleen M Schulze
  4. Dipika Desai
  5. Brian Kelly
  6. Russell J de Souza
  7. Guillaume Paré
  8. Deborah A Lawlor
  9. John Wright
  10. Sonia S Anand  Is a corresponding author
  1. McMaster University, Canada
  2. Bradford Royal Infirmary, United Kingdom
  3. University of Bristol, United Kingdom

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 alone, and 21.7% when combined with family history. A few weak PRS and GDM risk factors interactions modulating FPG and GDM were observed. 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.

Data availability

Data from START is not publicly available, since the study is bound by consent which indicates the data will not be used by an outside group. Requests for collaboration or replication will be considered for research purposes only (no commercial use allowed, as per the study's informed consent). Requests should be addressed to the study's principal investigator (Sonia Anand, anands@mcmaster.ca) via a form which will be provided upon request by emailing natcampb@mcmaster.ca. The request will be evaluated by PIs and co-investigators, and projects deemed of scientific interest will be further evaluated/validated by local REB chair. Born in Bradford data are available for research purposes only by sending an expression of interest form downloadable from https://borninbradford.nhs.uk/wp-content/uploads/BiB_EoI_v3.1_10.05.21.doct to borninbradford@bthft.nhs.uk . The proposal will be reviewed by BiB's executive team. If the request is approved, the requester will be asked to sign a Data Sharing Contract and a Data Sharing Agreement. Full details on how to access data and forms can be found here https://borninbradford.nhs.uk/research/how-to-access-data/. The code used to analyze the data is available at https://github.com/AmelLamri/Paper_T2dPrsGdm_StartBiB. All Sharable processed versions of the datasets used in the manuscript are made available as supplementary material or at https://github.com/AmelLamri/Paper_T2dPrsGdm_StartBiB.

Article and author information

Author details

  1. Amel Lamri

    Department of Medicine, McMaster University, Hamilton, Canada
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7182-0661
  2. Jayneel Limbachia

    Population Health Research Institute, McMaster University, Hamilton, Canada
    Competing interests
    No competing interests declared.
  3. Karleen M Schulze

    Population Health Research Institute, McMaster University, Hamilton, Canada
    Competing interests
    No competing interests declared.
  4. Dipika Desai

    Population Health Research Institute, McMaster University, Hamilton, Canada
    Competing interests
    No competing interests declared.
  5. Brian Kelly

    Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom
    Competing interests
    No competing interests declared.
  6. Russell J de Souza

    Population Health Research Institute, McMaster University, Hamilton, Canada
    Competing interests
    No competing interests declared.
  7. Guillaume Paré

    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6795-4760
  8. Deborah A Lawlor

    Population Health Science, University of Bristol, Bristol, United Kingdom
    Competing interests
    Deborah A Lawlor, has received support from Medtronic Ltd and Roche Diagnostics for research unrelated to that presented here. No financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work..
  9. John Wright

    Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom
    Competing interests
    No competing interests declared.
  10. Sonia S Anand

    Department of Medicine, McMaster University, Hamilton, Canada
    For correspondence
    anands@mcmaster.ca
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3692-7441

Funding

Canadian Institutes of Health Research (Project grant 298104;Foundation grant number: FDN-143255)

  • Sonia S Anand

Bristol NIHR Biomedical Research Center

  • Deborah A Lawlor

UK Medical Research Council (MC_UU_00011/6)

  • Deborah A Lawlor

British Heart Foundation (CH/F/20/90003)

  • Deborah A Lawlor

Canada Research Chairs

  • Sonia S Anand

Heart and Stroke Foundation/Michael G. DeGroote Chair

  • Sonia S Anand

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All START and BiB participants provided informed consent. The START study was approved by local ethics committees (Hamilton Integrated Research Ethics Board [ID:10-640], William Osler Health System [ID:11-0001], and Trillium Health Partners [RCC:11-018, ID:492]). Ethical approval for all aspects of the research was granted by Bradford Research Ethics Committee [Ref 07/H1302/112].

Reviewing Editor

  1. Edward D Janus, University of Melbourne, Australia

Publication history

  1. Received: June 30, 2022
  2. Preprint posted: July 16, 2022 (view preprint)
  3. Accepted: November 2, 2022
  4. Accepted Manuscript published: November 22, 2022 (version 1)
  5. Version of Record published: November 23, 2022 (version 2)

Copyright

© 2022, Lamri et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Amel Lamri
  2. Jayneel Limbachia
  3. Karleen M Schulze
  4. Dipika Desai
  5. Brian Kelly
  6. Russell J de Souza
  7. Guillaume Paré
  8. Deborah A Lawlor
  9. John Wright
  10. Sonia S Anand
(2022)
The genetic risk of gestational diabetes in South Asian women
eLife 11:e81498.
https://doi.org/10.7554/eLife.81498

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