The genetic risk of gestational diabetes in South Asian women
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/81498 |
| _version_ | 1811217573739495424 |
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| author | Amel Lamri Jayneel Limbachia Karleen M Schulze Dipika Desai Brian Kelly Russell J de Souza Guillaume Paré Deborah A Lawlor John Wright Sonia S Anand On behalf of for the Born in Bradford and START investigators |
| author_facet | Amel Lamri Jayneel Limbachia Karleen M Schulze Dipika Desai Brian Kelly Russell J de Souza Guillaume Paré Deborah A Lawlor John Wright Sonia S Anand On behalf of for the Born in Bradford and START investigators |
| author_sort | Amel Lamri |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T06:57:05Z |
| format | Article |
| id | doaj.art-63bd577f65be4d1b966ec2f8f5f48603 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T06:57:05Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-63bd577f65be4d1b966ec2f8f5f486032022-12-22T03:43:07ZengeLife Sciences Publications LtdeLife2050-084X2022-11-011110.7554/eLife.81498The genetic risk of gestational diabetes in South Asian womenAmel Lamri0https://orcid.org/0000-0001-7182-0661Jayneel Limbachia1Karleen M Schulze2Dipika Desai3Brian Kelly4Russell J de Souza5Guillaume Paré6https://orcid.org/0000-0002-6795-4760Deborah A Lawlor7John Wright8Sonia S Anand9https://orcid.org/0000-0003-3692-7441On behalf of for the Born in Bradford and START investigatorsDepartment of Medicine, McMaster University, Hamilton, Canada; Population Health Research Institute, Hamilton, CanadaPopulation Health Research Institute, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, CanadaPopulation Health Research Institute, Hamilton, CanadaPopulation Health Research Institute, Hamilton, CanadaBradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United KingdomPopulation Health Research Institute, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, CanadaPopulation 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, CanadaPopulation 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 KingdomBradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United KingdomDepartment of Medicine, McMaster University, Hamilton, Canada; Population Health Research Institute, Hamilton, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, CanadaSouth 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.https://elifesciences.org/articles/81498polygenic risk scoregestational diabetes mellitusType 2 diabetesSouth AsianBorn in BradfordSouth Asian birth cohort (START) |
| spellingShingle | Amel Lamri Jayneel Limbachia Karleen M Schulze Dipika Desai Brian Kelly Russell J de Souza Guillaume Paré Deborah A Lawlor John Wright Sonia S Anand On behalf of for the Born in Bradford and START investigators The genetic risk of gestational diabetes in South Asian women eLife polygenic risk score gestational diabetes mellitus Type 2 diabetes South Asian Born in Bradford South Asian birth cohort (START) |
| title | The genetic risk of gestational diabetes in South Asian women |
| title_full | The genetic risk of gestational diabetes in South Asian women |
| title_fullStr | The genetic risk of gestational diabetes in South Asian women |
| title_full_unstemmed | The genetic risk of gestational diabetes in South Asian women |
| title_short | The genetic risk of gestational diabetes in South Asian women |
| title_sort | genetic risk of gestational diabetes in south asian women |
| topic | polygenic risk score gestational diabetes mellitus Type 2 diabetes South Asian Born in Bradford South Asian birth cohort (START) |
| url | https://elifesciences.org/articles/81498 |
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