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The Genetic Architecture of Coronary Artery Disease: Current Knowledge and Future Opportunities

  • Genetics and Genomics (A. J. Marian, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

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.

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.

Summary

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.

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Acknowledgements

Work in the author’s laboratories is supported, in part, by NIH grants R01ES021801, R01ES021801-S3, R01ES025786, P01ES022845, R01MD010358, R01HL133169, and R01HL128572; U.S. EPA Grant RD83544101; a grant from the Whittier Foundation; and a Transatlantic

Networks of Excellence Award from Foundation Leducq. The funders had no role in preparation, review, or approval of the manuscript.

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Authors and Affiliations

  1. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, 90033, USA

    Jaana Hartiala, William S. Schwartzman, Julian Gabbay & Hooman Allayee

  2. Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, CA, 90033, USA

    Jaana Hartiala, William S. Schwartzman, Julian Gabbay & Hooman Allayee

  3. Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC202, Los Angeles, CA, 90033, USA

    Jaana Hartiala, William S. Schwartzman, Julian Gabbay & Hooman Allayee

  4. Department of Human Genetics, David Geffen School of Medicine of UCLA, Los Angeles, CA, 90095, USA

    Anatole Ghazalpour

  5. USDA Western Human Nutrition Research Center, University of California Davis, Davis, CA, 95616, USA

    Brian J. Bennett

  6. Department of Nutrition, University of California Davis, Davis, CA, 95616, USA

    Brian J. Bennett

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  1. Jaana Hartiala
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Hartiala, J., Schwartzman, W.S., Gabbay, J. et al. The Genetic Architecture of Coronary Artery Disease: Current Knowledge and Future Opportunities. Curr Atheroscler Rep 19, 6 (2017). https://doi.org/10.1007/s11883-017-0641-6

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