BGI Research, Shenzhen 518083, China.
Shenzhen Maternity & Child Healthcare Hospital, Shenzhen 518000, Guangdong, China.
Cell Genom. 2024 Oct 9;4(10):100657. doi: 10.1016/j.xgen.2024.100657.
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.
代谢物是健康和治疗靶点的关键指标，但它们在妊娠期间（人类生殖的关键时期）的遗传基础在很大程度上尚未得到探索。我们利用非侵入性产前检测的遗传数据，对 34394 名中国孕妇的 84 种代谢物（包括 37 种氨基酸、24 种元素、13 种激素和 10 种维生素）进行了全基因组关联研究，每个特定代谢物的样本量范围为 6394 到 13392。我们确定了 53 种代谢物-基因关联，其中 23 种是新的。这些关联中有 16.7%-100%观察到了妊娠和非妊娠妇女之间遗传效应的显著差异，表明存在基因-环境相互作用。此外，50.94%的遗传关联在代谢物之间以及六种代谢物和八种妊娠表型之间表现出了多效性。孟德尔随机化揭示了 7 种母体外周代谢物与 15 个人类特征和疾病之间的潜在因果关系。这些发现为妊娠期间母体血浆代谢物的遗传基础提供了新的见解。
