Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population

Eugene Lin, Yu-Ting Yan, Mu-Hong Chen, Albert C. Yang, Po-Hsiu Kuo () and Shih-Jen Tsai ()
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Eugene Lin: University of Washington
Yu-Ting Yan: National Taiwan University
Mu-Hong Chen: Taipei Veterans General Hospital
Albert C. Yang: National Yang Ming Chiao Tung University
Po-Hsiu Kuo: National Taiwan University
Shih-Jen Tsai: Taipei Veterans General Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract This pioneering genome-wide association study examined surrogate markers for insulin resistance (IR) in 147,880 Taiwanese individuals using data from the Taiwan Biobank. The study focused on two IR surrogate markers: the triglyceride to high-density lipoprotein cholesterol (TG:HDL-C) ratio and the TyG index (the product of fasting plasma glucose and triglycerides). We identified genome-wide significance loci within four gene clusters: GCKR, MLXIPL, APOA5, and APOC1, uncovering 197 genes associated with IR. Transcriptome-wide association analysis revealed significant associations between these clusters and TyG, primarily in adipose tissue. Gene ontology analysis highlighted pathways related to Alzheimer’s disease, glucose homeostasis, insulin resistance, and lipoprotein dynamics. The study identified sex-specific genes associated with TyG. Polygenic risk score analysis linked both IR markers to gout and hyperlipidemia. Our findings elucidate the complex relationships between IR surrogate markers, genetic predisposition, and disease phenotypes in the Taiwanese population, contributing valuable insights to the field of metabolic research.

Date: 2025
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DOI: 10.1038/s41467-025-58506-x

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