A Genome-Wide Association Study of Gestational Diabetes Mellitus in Korean Women
- Soo Heon Kwak1,
- Sung-Hoon Kim2,
- Young Min Cho1,
- Min Jin Go3,
- Yoon Shin Cho3,
- Sung Hee Choi1,
- Min Kyong Moon1,
- Hye Seung Jung1,
- Hyoung Doo Shin4,
- Hyun Min Kang5,
- Nam H. Cho6,
- In Kyu Lee7,
- Seong Yeon Kim1,
- Bok-Ghee Han3,
- Hak C. Jang1⇓ and
- Kyong Soo Park1,8⇓
- 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- 2Department of Medicine, Kwandong University College of Medicine, Seoul, Korea
- 3Center for Genome Science, Korea National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea
- 4Department of Life Science, Sogang University, Seoul, Korea
- 5Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
- 6Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea
- 7Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
- 8World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, Korea
- Corresponding authors: Hak C. Jang, , and Kyong Soo Park, .
Knowledge regarding the genetic risk loci for gestational diabetes mellitus (GDM) is still limited. In this study, we performed a two-stage genome-wide association analysis in Korean women. In the stage 1 genome scan, 468 women with GDM and 1,242 nondiabetic control women were compared using 2.19 million genotyped or imputed markers. We selected 11 loci for further genotyping in stage 2 samples of 931 case and 783 control subjects. The joint effect of stage 1 plus stage 2 studies was analyzed by meta-analysis. We also investigated the effect of known type 2 diabetes variants in GDM. Two loci known to be associated with type 2 diabetes had a genome-wide significant association with GDM in the joint analysis. rs7754840, a variant in CDKAL1, had the strongest association with GDM (odds ratio 1.518; P = 6.65 × 10−16). A variant near MTNR1B, rs10830962, was also significantly associated with the risk of GDM (1.454; P = 2.49 × 10−13). We found that there is an excess of association between known type 2 diabetes variants and GDM above what is expected under the null hypothesis. In conclusion, we have confirmed that genetic variants in CDKAL1 and near MTNR1B are strongly associated with GDM in Korean women. There seems to be a shared genetic basis between GDM and type 2 diabetes.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-1034/-/DC1.
- Received July 24, 2011.
- Accepted November 16, 2011.
- © 2012 by the American Diabetes Association.
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