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. [Display omitted] •23 novel genetic associations with maternal plasma metabolites in pregnancy•Pregnancy-specific genetic effects seen in 16.7%–100% of associations•Broad pleiotropy observed among metabolites and pregnant phenotypes•Potential causal relationships between 7 metabolites and 15 traits or diseases A large-scale genome-wide association study (GWAS) elucidates the genetic basis of 84 maternal plasma metabolites during pregnancy, identifying 53 metabolite-gene associations, of which 23 are novel. Pregnancy-specific genetic effects were found in 16.7%–100% of these associations. Pleiotropy was observed in 50.94% of the associations among metabolites and between six metabolites and eight pregnancy phenotypes. Potential causal relationships were identified between 7 maternal metabolites and 15 human traits or diseases.