孕期母体血浆代谢物的全基因组关联研究。

IF 11.1 Q1 CELL BIOLOGY Cell genomics Pub Date : 2024-10-09 DOI:10.1016/j.xgen.2024.100657
Siyang Liu, Jilong Yao, Liang Lin, Xianmei Lan, Linlin Wu, Xuelian He, Nannan Kong, Yan Li, Yuqing Deng, Jiansheng Xie, Huanhuan Zhu, Xiaoxia Wu, Zilong Li, Likuan Xiong, Yuan Wang, Jinghui Ren, Xuemei Qiu, Weihua Zhao, Ya Gao, Yuanqing Chen, Fengxia Su, Yun Zhou, Weiqiao Rao, Jing Zhang, Guixue Hou, Liping Huang, Linxuan Li, Xinhong Liu, Chao Nie, Liqiong Luo, Mei Zhao, Zengyou Liu, Fang Chen, Shengmou Lin, Lijian Zhao, Qingmei Fu, Dan Jiang, Ye Yin, Xun Xu, Jian Wang, Huanming Yang, Rong Wang, Jianmin Niu, Fengxiang Wei, Xin Jin, Siqi Liu
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引用次数: 0

摘要

代谢物是健康的关键指标和治疗靶点,但它们在孕期--人类生殖的关键时期--的遗传基础在很大程度上尚未被探索。利用无创产前检测的基因数据,我们对包括 37 种氨基酸、24 种元素、13 种激素和 10 种维生素在内的 84 种代谢物进行了全基因组关联研究,涉及 34,394 名中国孕妇,特定代谢物的样本量从 6,394 到 13,392 不等。我们发现了 53 种代谢物与基因的关联,其中 23 种是新发现的。在这些关联中,16.7%-100% 的遗传效应在孕妇和非孕妇之间存在显著差异,这表明基因与环境之间存在相互作用。此外,50.94%的基因关联在代谢物之间以及六种代谢物与八种妊娠表型之间表现出多效性。孟德尔随机化揭示了7种母体代谢物与15种人类特征和疾病之间的潜在因果关系。这些发现为研究孕期母体血浆代谢物的遗传基础提供了新的视角。
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Genome-wide association study of maternal plasma metabolites during pregnancy.

Metabolites are key indicators of health and therapeutic targets, but their genetic underpinnings during pregnancy-a critical period for human reproduction-are largely unexplored. Using genetic data from non-invasive prenatal testing, we performed a genome-wide association study on 84 metabolites, including 37 amino acids, 24 elements, 13 hormones, and 10 vitamins, involving 34,394 pregnant Chinese women, with sample sizes ranging from 6,394 to 13,392 for specific metabolites. We identified 53 metabolite-gene associations, 23 of which are novel. Significant differences in genetic effects between pregnant and non-pregnant women were observed for 16.7%-100% of these associations, indicating gene-environment interactions. Additionally, 50.94% of genetic associations exhibited pleiotropy among metabolites and between six metabolites and eight pregnancy phenotypes. Mendelian randomization revealed potential causal relationships between seven maternal metabolites and 15 human traits and diseases. These findings provide new insights into the genetic basis of maternal plasma metabolites during pregnancy.

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