Genetic architecture of plasma metabolome in 254,825 individuals.

ABSTRACT: Circulating metabolites are crucial to biological processes underlying health and diseases, yet their genetic determinants remain incompletely understood. Here, we investigate the genetic architecture of nuclear magnetic resonance-based metabolomics, analyzing 249 metabolic measures and 64 biologically plausible ratios in 254,825 participants. We conduct a genome-wide association study (GWAS) identifying 24,438 independent variant-metabolite associations across 427 loci, with effect sizes highly concordant with 19 previous studies. Fine-mapping pinpoints 3610 putative causal associations, 785 of which are novel. Additionally, we utilize whole exome sequencing data and uncover 2948 gene-metabolite associations through aggregate testing, underscoring the importance of rare coding variants ov

SUBMITTER: Qiang YX 

PROVIDER: S-EPMC12449471 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature