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.

中文翻译：

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妊娠期糖尿病和妊娠期葡萄糖代谢的遗传研究

审查目的

在这篇综述中，我们总结了妊娠期糖尿病 (GDM) 遗传学和妊娠期葡萄糖代谢的研究。我们在大量关于 2 型糖尿病 (T2D) 和血糖特征基因组学的文献的背景下描述了这些研究。

最近的发现

我们回顾了 GDM 的 23 项遗传关联研究并进行了荟萃分析，结果显示在 Bonferroni 校正后，8 个 T2D 位点的变异与 GDM 显着相关。这些研究表明 GDM 和 T2D 共享许多遗传风险位点。只有两项无偏见的全基因组关联研究 (GWAS) 成功揭示了 GDM 和妊娠期相关血糖特征的遗传关联。韩国女性 GDM 的 GWAS 确定了两个已知与 T2D 相关的基因座（靠近CDKAL1和MTNR1B），尽管MTNR1B基因座与 GDM的关联似乎强于 T2D。用于妊娠期血糖特征的多种族 GWAS 确定了两个新位点（靠近HKDC1和BACE2) 似乎与孕妇的负荷后血糖和空腹 c 肽有关。目前正在努力以多基因评分的形式使用这种遗传信息来预测 GDM 和产后 T2D 的风险。

概括

研究与 GDM 遗传关联的文献是有限的，尤其是与 T2D 和血糖特征基因组学的现有文献相比时。孕妇葡萄糖代谢的其他基因发现将需要更大的妊娠队列和国际合作努力。还需要对这些发现的临床意义进行研究。