Related Experiment Video

Updated: May 13, 2025

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

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GEO combined with quantitative protein trait loci identify causative proteins in hypertrophic cardiomyopathy

Bo Li1,2, Xu Zhao3, Yan Ding2

  • 1Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, China.

ESC Heart Failure
|May 10, 2025
PubMed

Insights

This study identified two proteins, carbonic anhydrase 3 (CA3) and serpin family E member 1 (SERPINE1), causally linked to hypertrophic cardiomyopathy (HCM). These findings offer potential new biomarkers and therapeutic targets for this rare genetic heart disease.

Area of Science:

  • Cardiovascular Genetics
  • Proteomics
  • Rare Diseases

Background:

  • Hypertrophic cardiomyopathy (HCM) is a rare genetic heart condition with limited research and treatment options.
  • Identifying novel therapeutic targets and biomarkers is crucial for managing HCM.
  • Integrating multi-omics data offers a powerful approach to uncover disease-associated mechanisms.

Purpose of the Study:

  • To identify proteins causally associated with hypertrophic cardiomyopathy (HCM).
  • To leverage integrated analysis of cardiac gene expression and proteomic data.
  • To explore potential therapeutic targets and diagnostic markers for HCM.

Main Methods:

  • Analysis of Gene Expression Omnibus (GEO) cardiac tissue datasets (GSE36961, GSE180313) from HCM patients and controls.
  • Integration with protein quantitative trait locus (pQTL) data from UK Biobank.
  • Genome-wide association study (GWAS) data from the FinnGen study for HCM.
  • Two-sample Mendelian randomization (MR) analysis to assess causal relationships.
  • Sensitivity analyses for heterogeneity and horizontal pleiotropy.

Main Results:

  • Two proteins, carbonic anhydrase 3 (CA3) and serpin family E member 1 (SERPINE1), were identified as causally associated with HCM risk.
  • Both CA3 and SERPINE1 showed a significant association with increased odds of developing HCM.
  • Analyses confirmed no significant heterogeneity or horizontal pleiotropy, supporting the robustness of the findings.

Conclusions:

  • CA3 and SERPINE1 proteins demonstrate a potential causal role in the development of HCM.
  • These proteins may serve as valuable characteristic markers for HCM diagnosis.
  • CA3 and SERPINE1 represent promising targets for future therapeutic interventions in HCM.
Abstract

Keywords:
Causal effectGene Expression Omnibus (GEO)Hypertrophic cardiomyopathyProtein quantitative trait loci (pQTL)

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