Where genome meets phenome: rationale for integrating genetic and protein biomarkers in the diagnosis and management of dilated cardiomyopathy and heart failure

J Am Coll Cardiol. 2012 Jul 24;60(4):283-9. doi: 10.1016/j.jacc.2012.05.005.


This review provides the rationale for integrating genomic and protein biomarkers in the evolving diagnosis and management of dilated cardiomyopathy (DCM) and its causal pathway to heart failure (HF), with a larger objective to serve as a template for genomic and phenomic profiling of other cardiovascular disease. DCM is a major cause of HF and accounts for more than half of heart transplantation in adults and children worldwide. DCM may remain asymptomatic for years, but HF and/or arrhythmias, both late manifestations of the disease, ultimately cause significant morbidity and mortality. A significant proportion of DCM has a genetic etiology. DCM can also result from environmental injury such as infection, toxins, or catecholamine excess. While molecular genetic testing can identify those at risk for genetic DCM, epigenetic and sentinel phenomic staging can help to identify those at highest risk in need for intervention. Phenomic staging includes integrating clinical and imaging features, transcriptomics, higher order proteomics and metabolomics interactions, and epidemiological data. This principle can be applied in family members of patients with DCM, where genetic testing and clinical phenotyping are indicated. This will allow the design of specific interventions tailored to individuals sharing similar risks, to alter the natural history of DCM and obviate complications such as HF/arrhythmias.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Animals
  • Biomarkers / blood*
  • Cardiomyopathy, Dilated / diagnosis*
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / therapy
  • Disease Progression
  • Epigenomics
  • Gene Expression Regulation / genetics
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study*
  • Heart Failure / diagnosis*
  • Heart Failure / genetics*
  • Heart Failure / therapy
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Matrix Metalloproteinases / blood
  • Mice
  • Natriuretic Peptide, Brain / blood
  • Precision Medicine
  • Proteomics
  • Receptors, Cell Surface / blood
  • Risk Assessment


  • Biomarkers
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Receptors, Cell Surface
  • Natriuretic Peptide, Brain
  • Matrix Metalloproteinases