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

Ming Ding, Jorge Chavarro, Sjurdur Olsen, Yuan Lin, Sylvia H. Ley, Wei Bao, Shristi Rawal, Louise G. Grunnet, Anne Cathrine B. Thuesen, James L. Mills, Edwina Yeung, Stefanie N. Hinkle, Wei Zhang, Allan Vaag, Aiyi Liu, Frank B. Hu, Cuilin Zhang

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1758-1768
Number of pages11
JournalDiabetologia
Volume61
Issue number8
DOIs
StatePublished - Aug 1 2018

Keywords

  • Genetic risk score
  • Genetic variants
  • Gestational diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Ding, M., Chavarro, J., Olsen, S., Lin, Y., Ley, S. H., Bao, W., Rawal, S., Grunnet, L. G., Thuesen, A. C. B., Mills, J. L., Yeung, E., Hinkle, S. N., Zhang, W., Vaag, A., Liu, A., Hu, F. B., & Zhang, C. (2018). Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations. Diabetologia, 61(8), 1758-1768. https://doi.org/10.1007/s00125-018-4637-8