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

Abstract

OBJECTIVE Gestational diabetes mellitus (GDM) is thought to have strong genetic basis. However, the knowledge regarding genetic risk factors of GDM is still limited. In this study, a genome-wide association analysis was performed in Korean women to identify genetic variants associated with GDM. In addition, the genetic susceptability of GDM was compared with that of type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS In stage 1 genome-scan, 468 GDM women and 1,242 non-diabetic control women were genotyped across 321,654 single nucleotide polymorphism (SNP) markers. Eleven suggestive loci were further genotyped in stage 2 samples of 931 cases and 783 controls. The joint effect of stage 1 + 2 studies were analyzed by meta-analysis using inverse-variance method. We also investigated the effect of known T2DM variants in the susceptability of GDM.

RESULTS Two loci known to be associated with T2DM showed genome-wide significant association with GDM in the joint analysis. A variant in CDKAL1 (cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1), rs7754840 C, showed the strongest association (odds ratio [OR] = 1.518, P = 6.65×10-16) with GDM. A variant in MTNR1B (melatonin receptor 1B), rs10830962 G, was also significantly associated with risk of GDM (OR = 1.454, P = 2.49×10-13). Both SNPs were associated with decreased fasting insulin concentration in GDM women. We found that there is an excess of association between known T2DM variants and GDM above what is expected under the null hypothesis. However, the association of rs10830962 G variant of MTNR1B was more significant in GDM compared to T2DM in Asians.

CONCLUSION Two genetic variants in CDKAL1 and MTNR1B were strongly associated with GDM in Korean women at a genome-wide significance level. Although there seems to be a similar genetic background between GDM and T2DM, variants in MTNR1B might confere differential effect.