ArticleNature genetics2025
Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Article
- Proteome-wide genetic analyses identify ASGR1 as a potential biomarker linking smoking with ischemic heart disease.Nature cardiovascular research · 2026Article
- Integrative analysis prioritizes proteins associated with renal cell carcinoma and its risk factors.JNCI cancer spectrum · 2026Article
- Endotrophin Measured by PRO-C6 as a Prognostic Biomarker for Liver-Related Events in Patients With Advanced Chronic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Protein mediators of chronic kidney disease in Type 2 diabetes: A mendelian randomization study.PLoS medicine · 2026Article
- An update on the landscape of collagen bioactive fragments.The FEBS journal · 2026Review
- Shared proteomic landscape between arteriosclerosis and cardiovascular endpoints: a Mendelian randomization and observational study integrating AlphaFold3 for structural prediction.Cardiovascular research · 2026Observational
- Genetic evidence prioritizes circulating proteins for heart failure beyond shared BMI-related genetic liability.medRxiv : the preprint server for health sciences · 2026Article
- Identifying druggable proteins of the association of chronotype on breast cancer using Mendelian randomization.Communications medicine · 2026Article
- Cardiovascular Genetic Epidemiology in the Genome-Wide Era: From Association Discovery to Mechanistic Dissection and Clinical Translation.Cardiovascular drugs and therapy · 2026Review
- Identifying circulating protein targets for common factors underlying schizophrenia, depression, and bipolar disorder.medRxiv : the preprint server for health sciences · 2026Article
- Plasma proteomic signatures of early retinal neurodegeneration in diabetes: A multi-cohort study.PLoS medicine · 2026Observational
- Colocalization and discordance between plasma and brain protein quantitative trait loci.bioRxiv : the preprint server for biology · 2026Article
- Low genetic risk for coronary artery disease underlies multigenerational longevity and healthy aging.GeroScience · 2026Article
- Characterization of a novel assay for full-length endotrophin in heart failure with preserved ejection fraction.Scientific reports · 2026Article
- Targeting COL6A3-C5 with nigericin suppresses endotrophin formation and enhances insulin sensitivity in obesity.Experimental & molecular medicine · 2026Article
- Article
- A resource of "bottom-line" variant associations for 1,281 complex traits by integrating data across published genome-wide association studies.Research square · 2026Article
- ProteoNexus: an integrative database to characterize genetic architecture, estimate mediation effects, and construct and evaluate prediction models of the plasma proteome.Nucleic acids research · 2026Article
- Circulating Plasma Proteins Influence the Risk of Aortic Dissection via Blood Pressure: A Network Mendelian Randomization and Multi-Omics Study.Journal of inflammation research · 2026Article
Corrections and comments
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Authors and funding
29 authors.
Funding
Abstract
Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3). COL6A3 levels were strongly increased by body mass index and increased coronary artery disease risk. Notably, the carboxyl terminus product of COL6A3, endotrophin, drove this effect. COL6A3 was highly expressed in disease-relevant cell types and tissues. Finally, we found that body fat reduction could reduce plasma levels of COL6A3-derived endotrophin, indicating a tractable way to modify endotrophin levels. In summary, we provide actionable insights into how circulating proteins mediate the effects of obesity on cardiometabolic diseases and prioritize endotrophin as a potential therapeutic target.
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