A Genome-Wide Association Study of Gestational Diabetes Mellitus in Korean Women

• DOI: 10.2337/db11-1034
• Publication Date: 2012-01-11T02:06:38Z
• Authors: Soo Heon Kwak; Sung-Hoon Kim; Young Min Cho; Min Jin Go; Yoon Shin Cho; Sung Hee Choi; Min Kyong Moon; Hye Seung Jung; Hyoung Doo Shin; Hyun Min Kang; Nam H. Cho; In Kyu Lee; Seong Yeon Kim; Bok-Ghee Han; Hak C. Jang; Kyong Soo Park
• Keywords: Adult; 0301 basic medicine; tRNA Methyltransferases; Korea; Receptor, Melatonin, MT1; Genetics/Genomes/Proteomics/Metabolomics; Cyclin-Dependent Kinase 5; Middle Aged; Polymorphism, Single Nucleotide; 3. Good health; Diabetes, Gestational; 03 medical and health sciences; Logistic Models; Diabetes Mellitus, Type 2; Pregnancy; Risk Factors; Humans; Female; Insulin Resistance; Aged; Genome-Wide Association Study

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.