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Genetic Studies of Gestational Diabetes and Glucose Metabolism in Pregnancy

  • Genetics (AP Morris, Section Editor)
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Abstract

Purpose of Review

In this review, we summarize studies investigating genetics of gestational diabetes mellitus (GDM) and glucose metabolism in pregnancy. We describe these studies in the context of the larger body of literature on type 2 diabetes (T2D) and glycemic trait genomics.

Recent Findings

We reviewed 23 genetic association studies for GDM and performed a meta-analysis, which revealed variants at eight T2D loci significantly associated with GDM after the Bonferroni correction. These studies suggest that GDM and T2D share a number of genetic risk loci. Only two unbiased genome-wide association studies (GWASs) have successfully revealed genetic associations for GDM and related glycemic traits in pregnancy. A GWAS for GDM in Korean women identified two loci (near CDKAL1 and MTNR1B) known to be associated with T2D, though the association of the MTNR1B locus with GDM appears to be stronger than that for T2D. A multi-ethnic GWAS for glycemic traits in pregnancy identified two novel loci (near HKDC1 and BACE2) which appear to be associated with post-load glucose and fasting c-peptide specifically in pregnant women. There are ongoing efforts to use this genetic information, in the form of polygenic scores, to predict risk of GDM and postpartum T2D.

Summary

The body of literature examining genetic associations with GDM is limited, especially when compared to the available literature on T2D and glycemic trait genomics. Additional genetic discovery for glucose metabolism in pregnant women will require larger pregnancy cohorts and international collaborative efforts. Studies on the clinical implications of these findings are also warranted.

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Funding

This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI15C3131) to S.H.K. C.E.P. is supported by NIH K23DK113218 and the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program.

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Authors and Affiliations

  1. Diabetes Unit, Endocrine Division, Massachusetts General Hospital, Boston, MA, USA

    Camille E. Powe

  2. Harvard Medical School, Boston, MA, USA

    Camille E. Powe

  3. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Camille E. Powe & Soo Heon Kwak

  4. Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Soo Heon Kwak

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  1. Camille E. Powe
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Correspondence to Soo Heon Kwak.

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Powe, C.E., Kwak, S.H. Genetic Studies of Gestational Diabetes and Glucose Metabolism in Pregnancy. Curr Diab Rep 20, 69 (2020). https://doi.org/10.1007/s11892-020-01355-3

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