Pleiotropic and sex-specific genetic mechanisms of circulating metabolic markers.

ABSTRACT: Metabolites in plasma form biosignatures of a range of common complex human diseases. Discovering variants with pleiotropic effects across metabolites can reveal underlying biological mechanisms. We therefore performed uni- and multivariate genome-wide association studies (GWAS) on 249 circulating metabolic markers across 328,006 UK Biobank and Estonian Biobank participants. We investigated rare variation through whole exome sequencing gene burden tests, analysed the role of body mass index through Mendelian randomization, and performed genome-wide interaction analyses with sex. We discovered 15,585 loci summed over the univariate GWAS, with high pleiotropy across markers, linked to a wide range of disorders. Findings from common and rare variant gene tests converged on lipid homeostasis p

SUBMITTER: van der Meer D 

PROVIDER: S-EPMC12119811 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature