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

Abstract

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.

Risk factors for gestational diabetes: is prevention possible?

“…We are aware of only one published GWAS of GDM to date. This was conducted among Korean women and demonstrated a potentially shared genetic basis between GDM and type 2 diabetes [9]. Emerging data also indicate a possible environmental aetiology for GDM.…”

Association of common polymorphisms with gestational diabetes mellitus in Japanese women: A case-control study

“…Our previous investigation has shown that women with Japanese GDM have beta cell dysfunction irrespective of presence or absence of overweight [25]. Regarding the genetic background, several studies revealed risk variants related to insulin secretion in Korean and Chinese population [36][37][38][39][40][41]. Of the three genetic variants found in this study, two are related to the regulation of insulin secretion (i.e.…”

“…The findings that maternal age at delivery, pre-pregnancy BMI and the rate of overweight were comparable between the GDM and NGT groups are important. Therefore, our study cohort is suitable to investigate GDM risk genes, as were suggested in previous reports [8,40].…”

Pregnancy Characteristics and Women’s Cardiovascular Health

“…For example, if it is found that genetic variants associated with high blood pressure and glucose intolerance/type 2 diabetes in general populations of men and nonpregnant women are also associated with HDP and GDM, this would lend some support to the hypothesis of a common etiology and pregnancy unmasking a preexisting (genetic) risk. There is some evidence that several type 2 diabetes mellitus variants from genome-wide association studies show robust associations with GDM (Karlsson et al 2007;Lauenborg et al 2009;Cho et al 2009;Kwak et al 2012). …”