▎ACHIEVEMENTS

A multidisciplinary research team from National Taiwan University (NTU) and other renowned institutions has made a significant breakthrough in understanding the genetic basis of insulin resistance (IR)—a key driver of metabolic and cardiovascular diseases. The study, published in Nature Communications, represents one of the most comprehensive genome-wide association studies ever conducted in an East Asian population.

Distinguished Professor Po-Hsiu Kuo of NTU, Professor Shih-Jen Tsai, Dr. Eugene Lin, and colleagues from other leading institutions formed the research team. They utilized data from the Taiwan Biobank to examine genetic variants associated with surrogate markers of insulin resistance in 147,880 Taiwanese adults. Two IR markers were used: the triglyceride-to-HDL-cholesterol (TG:HDL-C) ratio and the TyG index, calculated from fasting glucose and triglyceride levels.

Through large-scale genomic analysis, the team identified genome-wide significant associations across four gene clusters—GCKR, MLXIPL, APOA5, and APOC1—which play critical roles in lipid metabolism and glucose regulation. These findings reveal 197 genes linked to insulin resistance, providing new insights into how metabolic pathways are genetically regulated. Transcriptome-wide association studies further showed that these gene clusters are most active in adipose tissue, emphasizing the importance of fat metabolism in insulin signaling. Gene ontologyand pathway analyses indicated that these loci are involved not only in glucose homeostasis and lipid transport but also in neurodegenerative disease pathways, including Alzheimer’s disease. The study also identified sex-specific genetic effects, underscoring biological differences in how insulin resistance develops among men and women. Importantly, polygenic risk score analyses connected both IR markers to an increased predisposition to gout and hyperlipidemia, revealing overlapping genetic architectures among metabolic disorders.

Beyond its scientific contributions, this research exemplifies the growing impact of precision genomics in Taiwan. By integrating high-quality population data with advanced bioinformatics, NTU researchers demonstrated the value of the Taiwan Biobank as a powerful resource for uncovering disease mechanisms relevant to East Asian populations—groups that have been historically underrepresented in global genomic studies.

Professor Kuo emphasized that the study “not only enhances our understanding of the genetic architecture of insulin resistance but also opens pathways for developing ancestry-calibrated predictive tools for metabolic health.” Professor Tsai added that future work will focus on translating these discoveries into preventive and therapeutic strategies, particularly for conditions at the intersection of metabolism and brain health.

This landmark study underscores NTU’s leading role in advancing equitable precision medicine and highlights Taiwan’s growing contribution to global genomics and translational health research.