Related Experiment Video

Updated: Jul 16, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

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Predicted Deleterious Variants in Cardiomyopathy Genes Prognosticate Mortality and Composite Outcomes

Babken Asatryan1, Ravi A Shah2, Ghaith Sharaf Dabbagh3

  • 1Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

JACC. Heart Failure
|September 16, 2023
PubMed

Insights

Individuals with predicted deleterious variants in cardiomyopathy genes face higher risks of mortality and developing cardiomyopathy. Genetic screening identifies these risks in the general population, informing personalized health strategies.

Area of Science:

  • Cardiovascular Genetics
  • Genomics
  • Precision Medicine

Background:

  • Inherited cardiomyopathies exhibit diverse phenotypes, with limited data on genetic screening outcomes in the general population.
  • Understanding the impact of predicted deleterious variants in cardiomyopathy genes is crucial for risk stratification.

Purpose of the Study:

  • To assess the mortality and composite cardiomyopathy-related outcomes associated with predicted deleterious variants in cardiomyopathy-associated genes.
  • To analyze data from the UK Biobank for genetic screening strategies and outcomes.

Main Methods:

  • Whole exome sequencing data from UK Biobank participants were analyzed.
  • Variants in dilated, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy genes were annotated using REVEL and ANNOVAR.
  • Time-to-event analyses compared outcomes between genotype-positive and genotype-negative groups.

Main Results:

  • 2.64% of 200,619 participants (CMP-G+) carried predicted deleterious variants.
  • CMP-G+ individuals showed a higher risk of all-cause mortality (HR: 1.13) and diagnosis of cardiomyopathy (HR: 5.75).
  • A significantly elevated risk for composite outcomes (HR: 1.29) was observed in CMP-G+ individuals across all cardiomyopathy subgroups.

Conclusions:

  • Adults with predicted deleterious variants in cardiomyopathy genes have a slightly increased mortality risk.
  • These variants significantly elevate the risk of developing cardiomyopathy and related composite outcomes compared to controls.
Abstract

Keywords:
arrhythmogenic cardiomyopathycardiomyopathydilated cardiomyopathygeneticsgenotype-first approachhypertrophic cardiomyopathysudden cardiac death

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