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Diabetologia. 2018 Aug;61(8):1758-1768. doi: 10.1007/s00125-018-4637-8. Epub 2018 Jun 12.

Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations.

Author information

1
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
2
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
3
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
4
Centre for Fetal Programming, Statens Serum Institut, Copenhagen, Denmark.
5
Division of Intramural Population Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, 6710 Rockledge Dr, Bethesda, MD, 20817, USA.
6
Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA.
7
Department of Nutritional Sciences, School of Health Professions, Rutgers University, Newark, NJ, USA.
8
Department of Endocrinology, Rigshospitalet University Hospital, Copenhagen, Denmark.
9
AstraZeneca, Early Clinical Development and Innovative Medicines, Mölndal, Sweden.
10
Division of Intramural Population Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, 6710 Rockledge Dr, Bethesda, MD, 20817, USA. Zhangcu@mail.nih.gov.

Abstract

AIMS/HYPOTHESIS:

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse.

METHODS:

We conducted a case-control study among 2636 women with GDM and 6086 non-GDM control women from the Nurses' Health Study II and the Danish National Birth Cohort. A total of 112 susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for the false discovery rate.

RESULTS:

For the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1) and rs7041847 (GLIS3). In addition, we confirmed three variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B) and rs4506565 (TCF7L2), that had previously been significantly associated with GDM risk. Furthermore, compared with participants in the first (lowest) quartile of weighted GRS based on these 11 SNPs, the ORs for GDM were 1.07 (95% CI 0.93, 1.22), 1.23 (95% CI 1.07, 1.41) and 1.53 (95% CI 1.34, 1.74) for participants in the second, third and fourth (highest) quartiles, respectively. The significant positive associations between the weighted GRS and risk of GDM persisted across most of the strata of major risk factors for GDM, including family history of type 2 diabetes, smoking status, BMI and age.

CONCLUSIONS/INTERPRETATION:

In this large-scale case-control study with women from two independent populations, eight novel GDM SNPs were identified. These findings offer the potential to improve our understanding of the aetiology of GDM, and particularly of biological mechanisms related to beta cell function.

KEYWORDS:

Genetic risk score; Genetic variants; Gestational diabetes mellitus

PMID:
29947923
PMCID:
PMC6701842
DOI:
10.1007/s00125-018-4637-8
[Indexed for MEDLINE]
Free PMC Article

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