Format

Send to

Choose Destination
J Am Coll Cardiol. 2015 Mar 3;65(8):830-845. doi: 10.1016/j.jacc.2014.12.033.

Genome-wide significant loci: how important are they? Systems genetics to understand heritability of coronary artery disease and other common complex disorders.

Author information

1
Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York; Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia. Electronic address: johan.bjorkegren@mssm.edu.
2
Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
3
Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.

Abstract

Genome-wide association studies (GWAS) have been extensively used to study common complex diseases such as coronary artery disease (CAD), revealing 153 suggestive CAD loci, of which at least 46 have been validated as having genome-wide significance. However, these loci collectively explain <10% of the genetic variance in CAD. Thus, we must address the key question of what factors constitute the remaining 90% of CAD heritability. We review possible limitations of GWAS, and contextually consider some candidate CAD loci identified by this method. Looking ahead, we propose systems genetics as a complementary approach to unlocking the CAD heritability and etiology. Systems genetics builds network models of relevant molecular processes by combining genetic and genomic datasets to ultimately identify key "drivers" of disease. By leveraging systems-based genetic approaches, we can help reveal the full genetic basis of common complex disorders, enabling novel diagnostic and therapeutic opportunities.

KEYWORDS:

atherosclerosis; atherosclerotic plaque; genome-wide association study; myocardial infarction; primary prevention; regulatory gene networks

PMID:
25720628
PMCID:
PMC4374657
DOI:
10.1016/j.jacc.2014.12.033
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center