| Title: | Genetic regulation of insulin resistance surrogate index (TyG) and susceptibility to common diseases based on phenome-wide association study |
| Journal: | Molecular and Cellular Biochemistry |
| Published: | 13 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42126675/ |
| DOI: | https://doi.org/10.1007/s11010-026-05565-3 |
Publication 20055
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Abstract
Insulin resistance (IR) is a crucial driver of numerous metabolic and non-metabolic diseases, yet the associations between the triglyceride-glucose (TyG) index - a marker for IR - and a broad spectrum of health conditions remain poorly understood. A large-scale genome-wide association study (GWAS) of triglyceride-glucose (TyG) was performed based on over 320,000 Europeans in the UK Biobank. Then we used Mendelian randomization (MR) within the framework of a phenome-wide association study (PheWAS) and Multivariable Mendelian Randomization (MVMR) to investigate potential causal associations between TyG and clinical diseases and to explore genetic mechanisms through complex genetic approaches. GWAS identified a total of 166 independent single nucleotide polymorphisms (SNPs) with known functions in the regulation of adipogenesis and glucose energy metabolism, which are enriched in liver metabolic pathways. The MR-PheWAS study found causal associations between TyG and 9 clinical diseases. MVMR reveals a causal association between TyG and Hypertensive Heart Disease. Linkage disequilibrium score regression (LDSC) analysis further revealed genetic correlations between TyG and these diseases. PLACO analysis provided valuable insights into the potential mechanisms connecting TyG and common diseases. These findings enhance understanding of genetic determinants of TyG, clarify the underlying molecular mechanisms and causal relationships between TyG and common diseases, and guide future research toward potential interventions based on existing biomarkers and genetic insights.</p>
7 Authors
- Jia-Xin Wu
- Ling-Huan Bu
- Pei He
- Ming-Hui Xia
- Lin Bo
- Fei-Yan Deng
- Shu-Feng Lei
1 Application
| Application ID | Title |
|---|---|
| 76875 | Systematic Screening of Risk Factors for Bone and Joint Diseases |
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