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Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis
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Identification of PSMA4 as a Therapeutic Target for Atherosclerosis: A Comprehensive Multiomics Mendelian
Yongchao Yu1, Yuan Zhu2, Qian Tian2
1Comprehensive Ward, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Annals of Human Genetics
|April 25, 2026
Summary
This study identifies PSMA4 as a promising therapeutic target for atherosclerosis (AS). Genetic analysis confirms PSMA4
Area of Science:
- Genetics and Genomics
- Cardiovascular Disease Research
- Pharmacology and Drug Discovery
Background:
- Atherosclerosis (AS) is a major cause of cardiovascular disease.
- Current AS treatments lack efficacy in inducing plaque regression.
- Novel therapeutic targets are needed for effective AS drug development.
Purpose of the Study:
- To identify novel, genetically supported therapeutic targets for AS.
- To enable the development of more effective drugs for AS treatment.
Main Methods:
- Integrative multiomics framework utilizing summary-data-based Mendelian randomization (SMR).
- Combined GWAS, cis-eQTL, cis-mQTL, and cis-sQTL data for genetic association.
- Validation through two-sample MR, colocalization, LDSC, PheWAS, and scRNA-seq.
Main Results:
- PSMA4 nominated as a top candidate gene, consistently replicated across datasets.
- Confirmed causal effect of PSMA4 on AS risk with strong colocalization.
- PSMA4 expression in plaque immune cells and identified proteasome inhibitors as potential therapeutics.
Conclusions:
- PSMA4 is established as a promising therapeutic target for atherosclerosis.
- Robust genetic evidence supports PSMA4's role in AS pathogenesis.
- Potential for drug repurposing of existing proteasome inhibitors for AS treatment.
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