title: The Genetic Architecture of Coronary Artery Disease: Current Knowledge and Future Opportunities.
abstract: OBJECTIVE
  We provide an overview of our current understanding of the genetic architecture of coronary artery disease (CAD) and discuss areas of research that provide excellent opportunities for further exploration.
  
  
  RESULTS
  Large-scale studies in human populations, coupled with rapid advances in genetic technologies over the last decade, have clearly established the association of common genetic variation with risk of CAD. However, the effect sizes of the susceptibility alleles are for the most part modest and collectively explain only a small fraction of the overall heritability. By comparison, evidence that rare variants make a substantial contribution to risk of CAD has been somewhat disappointing thus far, suggesting that other biological mechanisms have yet to be discovered. Emerging data suggests that novel pathways involved in the development of CAD can be identified through complementary and integrative systems genetics strategies in mice or humans. There is also convincing evidence that gut bacteria play a previously unrecognized role in the development of CAD, particularly through metabolism of certain dietary nutrients that lead to proatherogenic metabolites in the circulation. A major effort is now underway to functionally understand the newly discovered genetic and biological associations for CAD, which could lead to the development of potentially novel therapeutic strategies. Other important areas of investigation for understanding the pathophysiology of CAD, including epistatic interactions between genes or with either sex and environmental factors, have not been studied on a broad scope and represent additional opportunities for future studies.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, 90033, USA.|Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, CA, 90033, USA.|Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC202, Los Angeles, CA, 90033, USA.
authors.forename: Jaana
authors.initials: J
authors.lastname: Hartiala
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, 90033, USA.|Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, CA, 90033, USA.|Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC202, Los Angeles, CA, 90033, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Schwartzman
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, 90033, USA.|Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, CA, 90033, USA.|Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC202, Los Angeles, CA, 90033, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Gabbay
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine of UCLA, Los Angeles, CA, 90095, USA.
authors.forename: Anatole
authors.initials: A
authors.lastname: Ghazalpour
authors.affiliation: USDA Western Human Nutrition Research Center, University of California Davis, Davis, CA, 95616, USA.|Department of Nutrition, University of California Davis, Davis, CA, 95616, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bennett
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA, 90033, USA. hallayee@usc.edu.|Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, CA, 90033, USA. hallayee@usc.edu.|Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC202, Los Angeles, CA, 90033, USA. hallayee@usc.edu.
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
mesh_terms: D000483:Alleles; D000818:Animals; D003324:Coronary Artery Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D012307:Risk Factors
keywords: Coronary artery disease; Gene-environment interactions; Genome-wide association study; Metabolomics; Microbiome; Rare variants