Next steps in cardiovascular disease genomic research--sequencing, epigenetics, and transcriptomics

TY - JOUR

T1 - Next steps in cardiovascular disease genomic research--sequencing, epigenetics, and transcriptomics

AU - Schnabel, Renate B

AU - Baccarelli, Andrea

AU - Lin, Honghuang

AU - Ellinor, Patrick T

AU - Benjamin, Emelia J

PY - 2012/1

Y1 - 2012/1

N2 - BACKGROUND: Genomic research in cardiovascular disease (CVD) has progressed rapidly over the last 5 years. In most cases, however, these groundbreaking observations have not yet been accompanied by clinically applicable tools for risk prediction, diagnosis, or therapeutic interventions.CONTENT: We reviewed the scientific literature published in English for novel methods and promising genomic targets that would permit large-scale screening and follow-up of recent genomic findings for CVD. We anticipate that advances in 3 key areas will be critical for the success of these projects. First, exome-centered and whole-genome next-generation sequencing will identify rare and novel genetic variants associated with CVD and its risk factors. Improvements in methods will also greatly advance the field of epigenetics and gene expression in humans. Second, research is increasingly acknowledging that static DNA sequence variation explains only a fraction of the inherited phenotype. Therefore, we expect that multiple epigenetic and gene expression signatures will be related to CVD in experimental and clinical settings. Leveraging existing large-scale consortia and clinical biobanks in combination with electronic health records holds promise for integrating epidemiological and clinical genomics data. Finally, a systems biology approach will be needed to integrate the accumulated multidimensional data.SUMMARY: Novel methods in sequencing, epigenetics, and transcriptomics, plus unprecedented large-scale cooperative efforts, promise to generate insights into the complexity of CVD. The rapid accumulation and integration of knowledge will shed light on a considerable proportion of the missing heritability for CVD.

AB - BACKGROUND: Genomic research in cardiovascular disease (CVD) has progressed rapidly over the last 5 years. In most cases, however, these groundbreaking observations have not yet been accompanied by clinically applicable tools for risk prediction, diagnosis, or therapeutic interventions.CONTENT: We reviewed the scientific literature published in English for novel methods and promising genomic targets that would permit large-scale screening and follow-up of recent genomic findings for CVD. We anticipate that advances in 3 key areas will be critical for the success of these projects. First, exome-centered and whole-genome next-generation sequencing will identify rare and novel genetic variants associated with CVD and its risk factors. Improvements in methods will also greatly advance the field of epigenetics and gene expression in humans. Second, research is increasingly acknowledging that static DNA sequence variation explains only a fraction of the inherited phenotype. Therefore, we expect that multiple epigenetic and gene expression signatures will be related to CVD in experimental and clinical settings. Leveraging existing large-scale consortia and clinical biobanks in combination with electronic health records holds promise for integrating epidemiological and clinical genomics data. Finally, a systems biology approach will be needed to integrate the accumulated multidimensional data.SUMMARY: Novel methods in sequencing, epigenetics, and transcriptomics, plus unprecedented large-scale cooperative efforts, promise to generate insights into the complexity of CVD. The rapid accumulation and integration of knowledge will shed light on a considerable proportion of the missing heritability for CVD.

KW - Cardiovascular Diseases/genetics

KW - Epigenesis, Genetic

KW - Exome

KW - Gene Expression Profiling

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genetic Research

KW - Genetic Variation

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Humans

KW - Sequence Analysis, DNA

KW - Systems Biology

U2 - 10.1373/clinchem.2011.170423

DO - 10.1373/clinchem.2011.170423

M3 - SCORING: Review article

C2 - 22100807

VL - 58

SP - 113

EP - 126

JO - CLIN CHEM

JF - CLIN CHEM

SN - 0009-9147

IS - 1

ER -