Into the Wild: GWAS Exploration of Non-coding RNAs

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 framew...

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Published in:Frontiers in cardiovascular medicine Vol. 5; p. 181
Main Authors: Giral, Hector, Landmesser, Ulf, Kratzer, Adelheid
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 17.12.2018
Subjects:
cardiometabolic disorders
Cardiovascular Medicine
coronary artery disease
genetic variant
GWAS
lncRNA
coronary artery disease
GWAS
lncRNA
genetic variant
cardiometabolic disorders
ISSN:2297-055X, 2297-055X
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Abstract 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 (CAD) 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 single-nucleotide polymorphisms (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.
AbstractList 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 (CAD) 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 single-nucleotide polymorphisms (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.
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 (CAD) 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 single-nucleotide polymorphisms (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.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 (CAD) 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 single-nucleotide polymorphisms (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.
Author Giral, Hector
Kratzer, Adelheid
Landmesser, Ulf
AuthorAffiliation 3 Berlin Institute of Health (BIH) , Berlin , Germany
1 Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin , Germany
2 DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin , Germany
AuthorAffiliation_xml – name: 3 Berlin Institute of Health (BIH) , Berlin , Germany
– name: 2 DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin , Germany
– name: 1 Department of Cardiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin , Germany
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  surname: Landmesser
  fullname: Landmesser, Ulf
– sequence: 3
  givenname: Adelheid
  surname: Kratzer
  fullname: Kratzer, Adelheid
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Keywords coronary artery disease
GWAS
lncRNA
genetic variant
cardiometabolic disorders
Language English
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Reviewed by: Baiba Vilne, Technische Universität München, Germany; Thorsten Kessler, Deutsches Herzzentrum München, Germany; Arne S. Schaefer, Charité Universitätsmedizin Berlin, Germany
Edited by: Jeanette Erdmann, Universität zu Lübeck, Germany
This article was submitted to Cardiovascular Genetics and Systems Medicine, a section of the journal Frontiers in Cardiovascular Medicine
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– volume: 115
  start-page: e11
  year: 2014
  ident: B34
  article-title: Recent developments in cardiovascular genetics and genomics
  publication-title: Circ Res
  doi: 10.1161/CIRCRESAHA.114.305054
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Snippet Genome-wide association studies (GWAS) have proven a fundamental tool to identify common variants associated to complex traits, thus contributing to unveil the...
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StartPage 181
SubjectTerms cardiometabolic disorders
Cardiovascular Medicine
coronary artery disease
genetic variant
GWAS
lncRNA
Title Into the Wild: GWAS Exploration of Non-coding RNAs
URI https://www.ncbi.nlm.nih.gov/pubmed/30619888
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