ArticleNature communications2025
Pleiotropic and sex-specific genetic mechanisms of circulating metabolic markers.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Divergent Patterns of Genetic Overlap Between Severe Mental Disorders and Metabolic Markers.The American journal of psychiatry · 2026Article
- Distinct metabolic signatures of Alzheimer's and Parkinson's disease revealed through genetic overlap.EBioMedicine · 2026Article
- Shared genetic architecture between anorexia nervosa and metabolomic biomarkers suggest underlying causal pathways.medRxiv : the preprint server for health sciences · 2025Article
- A genetic map of human metabolism across the allele frequency spectrum.Nature genetics · 2025Article
- Genetic architecture of plasma metabolome in 254,825 individuals.Nature communications · 2025Article
- Mapping the Genetic Landscape of Psychiatric Disorders With the MiXeR Toolset.Biological psychiatry · 2025Review
- Distinct metabolic signatures of Alzheimer's and Parkinson's disease revealed through genetic overlap with metabolic markers.medRxiv : the preprint server for health sciences · 2025Article
- Genome-wide association study for circulating metabolic traits in 619,372 individuals.medRxiv : the preprint server for health sciences · 2025Article
- Atlas of plasma metabolic markers linked to human brain morphology.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
27 authors.
Funding
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 pathways. 31 loci interacted with sex, mapped to genes involved in cholesterol processing. The findings offer insights into the genetic architecture of circulating metabolites, revealing pleiotropic loci, highlighting the role of rare variation, and uncovering sex-specific molecular mechanisms of lipid metabolism.
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