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From GWAS Hits to Treatment Targets

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Front. Cardiovasc. Med. | doi: 10.3389/fcvm.2018.00181

Into the wild: GWAS exploration of non-coding RNAs

Hector Giral1, Ulf Landmesser1 and  Adelheid Kratzer1*
  • 1Cardiology, CBF, Charité Universitätsmedizin Berlin, Germany

Genome-wide association studies (GWAS) have proven a fundamental tool to identify common variants associated to complex traits, thus contributing to unveil the genetic components of human disease. Besides, the advent of GWAS contributed to expose unexpected findings that urged to redefine the framework of population genetics. First, loci identified by GWAS had small effect sizes and could only explain a fraction of the predicted heritability of the traits under study. Second, the majority of GWAS hits mapped within non-coding regions (such as intergenic or intronic regions) where new functional RNA species (such as lncRNAs or circRNAs) have started to emerge. Bigger cohorts, meta-analysis and technical improvements in genotyping allowed identification of an increased number of genetic variants associated to coronary artery disease and cardiometabolic traits. The challenge remains to infer causal mechanisms by which these variants influence cardiovascular disease development. A tendency to assign potential causal variants preferentially to coding genes close to lead variants contributed to disregard the role of non-coding elements. In recent years, in parallel to an increased knowledge of the non-coding genome, new studies started to characterize disease-associated variants located within non-coding RNA regions. The upcoming of databases integrating SNPs and non-coding RNAs together with novel technologies will hopefully facilitate the discovery of causal non-coding variants associated to disease. This review attempts to summarize the current knowledge of genetic variation within non-coding regions with a focus on long non-coding RNAs that have widespread impact in cardiometabolic diseases.

Keywords: lincRNA, disease trait, Coronary Artery Disease, Cardiometabolic disorders, GWAS

Received: 05 Jul 2018; Accepted: 03 Dec 2018.

Edited by:

Jeanette Erdmann, Universität zu Lübeck, Germany

Reviewed by:

Thorsten Kessler, Deutsches Herzzentrum München, Germany
Baiba Vilne, Technische Universität München, Germany
Arne S. Schaefer, Charité Medical University of Berlin, Germany  

Copyright: © 2018 Giral, Landmesser and Kratzer. 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(s) 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: Dr. Adelheid Kratzer, Charité Universitätsmedizin Berlin, Cardiology, CBF, Berlin, 8952, Germany, adelheid.kratzer@charite.de