Multi‐tissue transcriptome‐wide association study reveals susceptibility genes and drug targets for insulin resistance‐relevant phenotypes
Authors' conclusion
Our study provided new insights into IR aetiology and avenues for therapeutic development.
Study context
- Population
- Largest genome-wide association studies (GWAS) summary statistics for insulin resistance (IR) (Insulin Sensitivity Index, HOMA-IR, fasting insulin) and lipid-relevant traits (HDL-C, TG, LDL-C, total cholesterol)
- Outcome
- Susceptibility genes for IR-relevant phenotypes
Methodological detailsmulti-tissue, 49 human tissues, conditional and joint analyses, Mendelian randomization causal inference analysis
- Multi-tissue
- 49 human tissues
- Conditional and joint analyses
- Mendelian randomization causal inference analysis
Main finding
As reported in the abstract
Susceptibility genes causally associated with IR-relevant phenotypes
- Susceptibility genes causally associated with IR-relevant phenotypes
- 1190
- Genes not implicated in the original GWAS
- 58
- Genes further supported in differential expression analyses or a gene knockout mice database (e.g. KRIT1)
- 11
- Proteins encoded by susceptibility genes targeted by clinically approved drugs
- 7
- Genes already drug targets for IR-related diseases/traits (H6PD, CACNB2, DRD2)
- 3
- Compounds from drug repurposing analysis with profiles opposing IR-risk gene expression
- 4
Original publication
Multi‐tissue transcriptome‐wide association study reveals susceptibility genes and drug targets for insulin resistance‐relevant phenotypes. Diabetes Obes Metab. Published 1 October 2023. doi:10.
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