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Novel insights into the genetic architecture of pregnancy glycemic traits from 14,744 Chinese maternities

Huanhuan Zhu,Han Xiao,Linxuan Li,Meng Yang,Ying Lin,Jieqiong Zhou,Xinyi Zhang,Yan Zhou,Xianmei Lan,Jiuying Liu,J. Zeng,Lin Wang,Y. Zhong,X. Qian,Z. Cao,Panhong Liu,H. Mei,M. Cai,X. Cai,Zhuangyuan Tang,Liqin Hu,Rui Zhou,Xun Xu,Huanming Yang,Jian Wang,Xin Jin,Aifen Zhou

Published 2024 in Cell Genomics

ABSTRACT

Summary Glycemic traits are critical indicators of maternal and fetal health during pregnancy. We performed genetic analysis for five glycemic traits in 14,744 Chinese pregnant women. Our genome-wide association study identified 25 locus-trait associations, including established links between gestational diabetes mellitus (GDM) and the genes CDKAL1 and MTNR1B. Notably, we discovered a novel association between fasting glucose during pregnancy and the ESR1 gene (estrogen receptor), which was validated by an independent study in pregnant women. The ESR1-GDM link was recently reported by the FinnGen project. Our work enhances the findings in East Asian populations and highlights the need for independent studies. Further analyses, including genetic correlation, Mendelian randomization, and transcriptome-wide association studies, provided genetic insights into the relationship between pregnancy glycemic traits and hypertension. Overall, our findings advance the understanding of genetic architecture of pregnancy glycemic traits, especially in East Asian populations.

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