Location: Obesity and Metabolism ResearchTitle: The genetic architecture of coronary artery disease: current knowledge and future opportunities
|HARTIALA, JAANA - University Of Southern California
|SCHWARTZMAN, WILLIAM - University Of Southern California
|GABBAY, JULIAN - University Of Southern California
|GHAZALPOUR, ANATOLE - University Of Southern California
|ALLAYEE, HOOMAN - University Of Southern California
Submitted to: Current Atherosclerosis Reports
Publication Type: Review Article
Publication Acceptance Date: 1/31/2016
Publication Date: 1/31/2017
Citation: Hartiala, J., Schwartzman, W.S., Gabbay, J., Ghazalpour, A., Bennett, B.J., Allayee, H. 2017. The genetic architecture of coronary artery disease: current knowledge and future opportunities. Current Atherosclerosis Reports. 19(2):6. doi: 10.1007/s11883-017-0641-6.
Interpretive Summary: A major effort is now underway to functionally understand the newly discovered genetic and biological associations for Coronary artery disease (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.
Technical Abstract: Recent Findings 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.