Diabetes Metab J.
2025 Jan;49(1):128-143. 10.4093/dmj.2024.0139.
Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women
- Tam CHt
1,2,3 - Wang Y4
- Wang CC5,6,7,8
- Yuen LY5
- Lim CKp1,2,3
- Leng J9
- Wu L5
- Ng ACw1
- Hou Y1
- Tsoi KY1
- Wang H10
- Ozaki R1,2
- Li AM11
- Wang Q12
- Chan JCn1,2,3,13
- Ye YC14
- Tam WH5
- Yang X10
- Ma RCw1,2,3,13
- Affiliations
-
- 1Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- 2Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China
- 3CUHK-SJTU Joint Research Center in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China
- 4Scientific Research Platform of the Second School of Clinical Medicine, Guangdong Medical University, Dongguan, China
- 5Department of Obstetrics and Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- 6Development and Reproduction Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
- 7School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China
- 8Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong, China
- 9Department of Children’s Health, Tianjin Women and Children’s Health Center, Tianjin, China
- 10Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China
- 11Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
- 12Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- 13Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
- 14Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
- KMID: 2563275
- DOI: http://doi.org/10.4093/dmj.2024.0139
Abstract
- Background
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.
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