Abstract
OBJECTIVE Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes (T2D). It remains unclear whether genetic information improves prediction of incident T2D in these women. RESEARCH DESIGN AND METHODS Using five independent cohorts representing four different ancestries (n = 1,895), we investigated whether a genome-wide T2D polygenic risk score (PRS) is associated with increased risk of incident T2D. We also calculated the area under the receiver operating characteristics curve (AUROC) and continuous net reclassification improvement (NRI) following the incorporation of T2D PRS into clinical risk models to assess the diagnostic utility. RESULTS Among 1,895 women with previous history of GDM, 363 (19.2%) developed T2D in a range of 2 to 30 years. T2D PRS was higher in those who developed T2D (-0.08 vs. 0.31, P = 2.3 × 10-11) and was associated with an increased risk of incident T2D (odds ratio 1.52 per 1-SD increase, 95% CI 1.05–2.21, P = 0.03). In a model that includes age, family history of diabetes, systolic blood pressure, and BMI, the incorporation of PRS led to an increase in AUROC for T2D from 0.71 to 0.74 and an intermediate improvement of NRI (0.32, 95% CI 0.15–0.49, P = 3.0 × 10-4). Although there was variation, a similar trend was observed across study cohorts. CONCLUSIONS In cohorts of GDM women with diverse ancestry, T2D PRS was significantly associated with future development of T2D. A significant but small improvement was observed in AUROC when T2D PRS was integrated into clinical risk models to predict incident T2D.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1622-1629 |
| Number of pages | 8 |
| Journal | Diabetes care |
| Volume | 47 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2024 |
Funding
Acknowledgments. The authors thank the participants and staff of the UKBB and Seoul National University T2D cohort for their dedication and contribution to the research. The authors also thank the members of the Diabetes Polygenic RIsk Scores in Multiple Ancestries (D-PRISM) study in the Polygenic Risk Methods in Diverse Populations (PRIMED) consortium for their support. This research was conducted using the UKBB resource under application no. 91312 and bioresources from the National Biobank of Korea, the Center for Disease Control and Prevention, Republic of Korea (NBK-2021-015). Funding. This study was supported by a grant from the National Human Genome Research Institute (U01HG011723), the National Research Foundation of Korea grant funded by the Korean Ministry of Science and ICT (RS-2023-00262002), and by a Ministry of Food and Drug Safety grant (23212MFDS202) in 2023 awarded to S.H.K. H.L. was supported by the MD-PhD/Medical Scientist Training Program through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea, and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1A6A1A03047972). A.K., D.M.S., and W.L.L. were supported by grants U01DK094830 from the National Institute of Diabetes and Digestive and Kidney Diseases and R01-HD-34242 and R01-HD-34243 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. A.H.-C. was supported by the American Diabetes Association grant 11-23-PDF-35. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. J.C. and S.H.K. researched, analyzed, and interpreted the data and wrote the manuscript. J.C., H.L., A.K., A.H.-C., D.C., and M.H. performed statistical analysis and reviewed the manuscript. A.H.-C., D.M.S., W.L.L., H.C.J., and K.S.P. collected data and reviewed the manuscript. A.K.M. reviewed the manuscript. All authors approved the final version of the manuscript. J.C. and S.H.K. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Part of this study was presented orally at the 82nd Scientific Sessions of the American Diabetes Association, New Orleans, LA, 3\u20137 June 2022, and the 75th Annual Meeting of the American Society of Human Genetics, Washington, DC, 1\u20135 November 2023. This work was supported by Ministry of Food and Drug Safety, Ministry of Science and ICT of Korea; Seoul National University Hospital; and NIH/NHGRI
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Advanced and Specialized Nursing
