Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 65, Issue 8, Pages 830-845Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2014.12.033
Keywords
atherosclerosis; atherosclerotic plaque; genome-wide association study; myocardial infarction; primary prevention; regulatory gene networks
Categories
Funding
- American Heart Association [14SFRN20490315, 14SFRN20840000]
- Leducq Foundation (Transatlantic Network of Excellence Awards)
- Swedish Heart-Lung Foundation
- Swedish Research Council
- University of Tartu (SP1GVARENG)
- Estonian Research Council
- AstraZeneca Translational Science Centre-Karolinska Institutet
- National Institutes of Health [K08HL111330, R01 DK098242, U54 CA189201]
- AstraZeneca
- PhRMA Foundation
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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. (C) 2015 by the American College of Cardiology Foundation.
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