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April 26, 2026Annals of Human Genetics

Identification of PSMA4 as a Therapeutic Target for Atherosclerosis: A Comprehensive Multiomics Mendelian Randomization Analysis

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Authors

YYYongchao YuYZYuan ZhuQTQian Tian

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Overview

Randomized trial identifies PSMA4 as a causal target for atherosclerosis, suggesting new treatment options.

Key Points

  • The study aims to identify new therapeutic targets for atherosclerosis using a multiomics approach.
  • Utilized summary-data-based mendelian randomization (SMR) to evaluate druggable genes and atherosclerosis (AS).
  • Combined genome-wide association study (GWAS) data with blood cis-expression quantitative trait loci (cis-eQTL) from three independent cohorts.
  • Validated candidates using external datasets, colocalization, and linkage disequilibrium score regression (LDSC).
  • PSMA4 was identified as a promising target with a strong causal effect on atherosclerosis risk (PP.H4 = 0.941).
  • Multiomics analyses showed that methylation and splicing sites of PSMA4 regulate its expression affecting AS risk.
  • PheWAS indicated a safe profile for PSMA4-related targets, with high expression found in immune cells within plaques.

Cite This Study

Yu et al. (2026) studied this question.

synapsesocial.com/papers/69edacdb4a46254e215b498ahttps://doi.org/10.1111/ahg.70039
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