Related Experiment Video

Updated: Aug 10, 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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Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic

Rafik Tadros1,2,3, Sean L Zheng4,5,6, Christopher Grace7,8

  • 1Cardiovascular Genetics Centre, Montreal Heart Institute, Montreal, QC, Canada.

Medrxiv : the Preprint Server for Health Sciences
|February 13, 2023
PubMed

Insights

This study identified 70 genetic loci linked to hypertrophic cardiomyopathy (HCM), a heart condition. A novel gene, SVIL, was found to cause HCM, offering new insights into disease mechanisms and potential treatments.

Area of Science:

  • Genetics
  • Cardiology
  • Molecular Biology

Background:

  • Hypertrophic cardiomyopathy (HCM) is a significant cause of heart disease morbidity and mortality.
  • Both monogenic and polygenic factors contribute to HCM development.
  • Understanding the genetic architecture of HCM is crucial for improving diagnosis and treatment.

Approach:

  • Conducted the largest genome-wide association study (GWAS) for HCM, including 5,900 cases and 68,359 controls.
  • Utilized multi-trait analysis (MTAG) and cardiac magnetic resonance (CMR) imaging data from 36,083 UK Biobank participants.
  • Integrated genetic data with phenotypic information to identify novel disease-associated loci and genes.

Key Points:

  • Identified 70 loci associated with HCM (50 novel) and 62 loci for left ventricular (LV) traits (32 novel).
  • Discovered a novel HCM gene, SVIL, demonstrating that rare truncating variants in SVIL cause HCM.
  • Mendelian randomization supported a causal role for increased LV contractility in HCM pathogenesis.

Conclusions:

  • The study significantly expands the understanding of the genetic basis of hypertrophic cardiomyopathy.
  • Identification of SVIL as an HCM gene provides a new molecular target for research.
  • Findings suggest shared mechanisms and potential for unified therapeutic strategies across HCM subtypes.

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