ArticleNature communications2025
Multivariate genome-wide analyses of insulin resistance unravel novel loci and therapeutic targets for cardiometabolic health.
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 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed.
- From GWAS Signals to Molecular Mechanisms: Explainable AI for Causal Gene Prioritization and Biomolecular Target Interpretation.Biomolecules · 2026Review
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- Interplay Between Fibroblast Growth Factor-19, Beta-Klotho, and Receptors Impacts Cardiovascular Risk in Chronic Kidney Disease.Journal of clinical medicine · 2026Article
- Genetics-guided screening and biological validation identify zeylenol as a promising EGFR inhibitor in glioma.Frontiers in genetics · 2026Article
- Multivariate genome-wide analyses of insulin resistance unravel novel loci and therapeutic targets for cardiometabolic health.Nature communications · 2025Article
- Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Limited identification of insulin resistance-associated loci hinders understanding of its role in cardiometabolic health, impeding therapeutic strategies. We apply three multivariate genome-wide association study approaches on homeostatic model assessment for insulin resistance, insulin resistance index, fasting insulin, and ratio of triglycerides to high-density lipoprotein cholesterol from MAGIC and UK Biobank to develop a comprehensive phenotype ('mvIR'), and identify 217 independent loci, including 24 novel loci. The mvIR is causally associated with higher risks of 17 cardiometabolic diseases and five aging phenotypes, independent of adiposity and sarcopenia. We outline 21 of 2644 druggable genes for insulin resistance by Mendelian randomization and colocalization, where six genes (AKT1, ERBB3, FCGR1A, FGFR1, LPL, NR1H3) encode targets for approved drugs with consistent directions in alleviating insulin resistance, with no significant side effects revealed by phenome-wide association study. This study uncovers novel loci and therapeutic targets to inform strategies promoting insulin resistance-centered cardiometabolic health and longevity.
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Registered trials
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