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From GWAS Hits to Treatment Targets

Mini Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cardiovasc. Med. | doi: 10.3389/fcvm.2018.00072

GWAS reveal targets in vessel wall pathways to treat coronary artery disease

  • 1Center for Public Health Genomics, University of Virginia, United States
  • 2Biochemistry and Molecular Genetics, University of Virginia, United States
  • 3Data Science Institute, University of Virginia, United States
  • 4Department of Public Health Sciences, University of Virginia, United States

Coronary artery disease (CAD) is the leading cause of mortality worldwide and poses a considerable public health burden. Recent genome-wide association studies (GWAS) have revealed >100 genetic loci associated with CAD susceptibility in humans. While a number of these loci harbor gene targets of currently approved therapies, such as statins and PCSK9 inhibitors, the majority of the annotated genes at these loci encode for proteins involved in vessel wall function with no known drugs available. Importantly many of the associated genes linked to vascular (smooth muscle, endothelial, and macrophage) cell processes are now organized into distinct functional pathways, e.g. vasodilation, growth factor responses, extracellular matrix and plaque remodeling, and inflammation. In this mini-review, we highlight the most recently identified loci that have predicted roles in the vessel wall and provide genetic context for pre-existing therapies as well as new drug targets informed from GWAS. With the development of new modalities to target these pathways, (e.g. antisense oligonucleotides, CRISPR/Cas9, and RNA interference) as well as the computational frameworks to prioritize or reposition therapeutics, there is great opportunity to close the gap from initial genetic discovery to clinical translation for many patients affected by this common disease.

Keywords: genome-wide association study (GWAS), Coronary artery disease (CAD), Drug Targets, smooth muscle cells, vascular wall

Received: 22 Mar 2018; Accepted: 29 May 2018.

Edited by:

Jeanette Erdmann, Universität zu Lübeck, Germany

Reviewed by:

Yun Fang, University of Chicago, United States
Hsiao-Huei Chen, University of Ottawa, Canada  

Copyright: © 2018 Turner, Wong, Dreisbach and Miller. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Clint L. Miller, University of Virginia, Center for Public Health Genomics, PO Box 800717, Charlottesville, 22908, Virginia, United States, clintm@stanford.edu