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

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...

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Main Authors: Eugene Lin, Yu-Ting Yan, Mu-Hong Chen, Albert C. Yang, Po-Hsiu Kuo, Shih-Jen Tsai
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58506-x
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author Eugene Lin
Yu-Ting Yan
Mu-Hong Chen
Albert C. Yang
Po-Hsiu Kuo
Shih-Jen Tsai
author_facet Eugene Lin
Yu-Ting Yan
Mu-Hong Chen
Albert C. Yang
Po-Hsiu Kuo
Shih-Jen Tsai
author_sort Eugene Lin
collection DOAJ
description 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.
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spelling doaj-art-b932ecf096a94e47886ed2aa3656fc362025-08-20T03:52:19ZengNature PortfolioNature Communications2041-17232025-04-0116111410.1038/s41467-025-58506-xGene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank populationEugene Lin0Yu-Ting Yan1Mu-Hong Chen2Albert C. Yang3Po-Hsiu Kuo4Shih-Jen Tsai5Department of Genome Sciences, University of WashingtonDepartment of Public Health & Institute of Epidemiology and Preventive Medicine, National Taiwan UniversityDepartment of Psychiatry, Taipei Veterans General HospitalBrain Research Center, National Yang Ming Chiao Tung UniversityDepartment of Public Health & Institute of Epidemiology and Preventive Medicine, National Taiwan UniversityDepartment of Psychiatry, Taipei Veterans General HospitalAbstract 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.https://doi.org/10.1038/s41467-025-58506-x
spellingShingle Eugene Lin
Yu-Ting Yan
Mu-Hong Chen
Albert C. Yang
Po-Hsiu Kuo
Shih-Jen Tsai
Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population
Nature Communications
title Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population
title_full Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population
title_fullStr Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population
title_full_unstemmed Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population
title_short Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population
title_sort gene clusters linked to insulin resistance identified in a genome wide study of the taiwan biobank population
url https://doi.org/10.1038/s41467-025-58506-x
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