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01.02.2017 | Genetics and Genomics (A. J. Marian, Section Editor)

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

verfasst von: Jaana Hartiala, William S. Schwartzman, Julian Gabbay, Anatole Ghazalpour, Brian J. Bennett, Hooman Allayee

Erschienen in: Current Atherosclerosis Reports | Ausgabe 2/2017

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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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Titel: The Genetic Architecture of Coronary Artery Disease: Current Knowledge and Future Opportunities
verfasst von: Jaana Hartiala
William S. Schwartzman
Julian Gabbay
Anatole Ghazalpour
Brian J. Bennett
Hooman Allayee
Publikationsdatum: 01.02.2017
Verlag: Springer US
Erschienen in: Current Atherosclerosis Reports / Ausgabe 2/2017
Print ISSN: 1523-3804
Elektronische ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-017-0641-6

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

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