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From GWAS Hits to Treatment Targets

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Front. Cardiovasc. Med. | doi: 10.3389/fcvm.2018.00025

Integrative bioinformatics approaches for identification of drug targets in hypertension

 Daiane Hemerich1, 2, Jessica van Setten1,  Vinicius Tragante1 and  Folkert W. Asselbergs1, 3, 4, 5*
  • 1Department of Cardiology, University Medical Center Utrecht, Netherlands
  • 2Coordenação de Aperfeicoamento de Pessoal de Nível Superior, Brazil
  • 3Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Netherlands
  • 4Institute of Cardiovascular Science, University College London, United Kingdom
  • 5Farr Institute of Health Informatics Research and Institute of Health Informatics, University College London, United Kingdom

High blood pressure or hypertension is an established risk factor for a myriad of cardiovascular diseases. Genome-wide association studies have successfully found over nine hundred loci that contribute to blood pressure. However, the mechanisms through which these loci contribute to disease are still relatively undetermined as less than 10% of hypertension-associated variants are located in coding regions. Phenotypic cell-type specificity analyses and expression quantitative trait loci show predominant vascular and cardiac tissue involvement for blood pressure-associated variants. Maps of chromosomal conformation and expression quantitative trait loci (eQTL) in critical tissues identified 2424 genes interacting with blood pressure-associated loci, of which 517 are druggable. Integrating genome, regulome and transcriptome information in relevant cell-types could help to functionally annotate blood pressure associated loci and identify drug targets.

Keywords: Hypertension, Blood Pressure, Epigenetic regulation, GWAS, data integration, functional annotation, Drug target identification

Received: 19 Jan 2018; Accepted: 12 Mar 2018.

Edited by:

Jeanette Erdmann, University of Lübeck, Germany

Reviewed by:

PALLAVI R. DEVCHAND, Icahn School of Medicine at Mount Sinai, United States
Melanie Boerries, Deutsches Krebsforschungszentrum (DKFZ), Germany
Yuqi Zhao, University of California, Los Angeles, United States  

Copyright: © 2018 Hemerich, van Setten, Tragante and Asselbergs. 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. Folkert W. Asselbergs, University Medical Center Utrecht, Department of Cardiology, Utrecht, Netherlands,