Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits

Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results...

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Autores:
Tipo de recurso:
Fecha de publicación:
2019
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/24006
Acceso en línea:
https://doi.org/10.1038/s41431-018-0295-z
https://repository.urosario.edu.co/handle/10336/24006
Palabra clave:
Allele
Article
Cohort analysis
Computer model
Dutchman
Electrocardiogram
Exon
Follow up
Gene frequency
Gene locus
Gene mapping
Genome
Genome-wide association study
Genotype
Heart rate
Human
Major clinical study
Meta analysis
Netherlands
Priority journal
Qrs interval
Qt interval
Quantitative trait
Rr interval
Sample
Single nucleotide polymorphism
Rights
License
Abierto (Texto Completo)
id EDOCUR2_aa5f7e6b0d41c0ca1f003e2d9a898e1e
oai_identifier_str oai:repository.urosario.edu.co:10336/24006
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.spa.fl_str_mv Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
title Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
spellingShingle Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
Allele
Article
Cohort analysis
Computer model
Dutchman
Electrocardiogram
Exon
Follow up
Gene frequency
Gene locus
Gene mapping
Genome
Genome-wide association study
Genotype
Heart rate
Human
Major clinical study
Meta analysis
Netherlands
Priority journal
Qrs interval
Qt interval
Quantitative trait
Rr interval
Sample
Single nucleotide polymorphism
title_short Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
title_full Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
title_fullStr Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
title_full_unstemmed Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
title_sort Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
dc.subject.keyword.spa.fl_str_mv Allele
Article
Cohort analysis
Computer model
Dutchman
Electrocardiogram
Exon
Follow up
Gene frequency
Gene locus
Gene mapping
Genome
Genome-wide association study
Genotype
Heart rate
Human
Major clinical study
Meta analysis
Netherlands
Priority journal
Qrs interval
Qt interval
Quantitative trait
Rr interval
Sample
Single nucleotide polymorphism
topic Allele
Article
Cohort analysis
Computer model
Dutchman
Electrocardiogram
Exon
Follow up
Gene frequency
Gene locus
Gene mapping
Genome
Genome-wide association study
Genotype
Heart rate
Human
Major clinical study
Meta analysis
Netherlands
Priority journal
Qrs interval
Qt interval
Quantitative trait
Rr interval
Sample
Single nucleotide polymorphism
description Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits: PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency less than 5%). In addition to many known loci, we identified seven novel locus-trait associations: KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes. © 2019, The Author(s).
publishDate 2019
dc.date.created.spa.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2020-05-26T00:07:29Z
dc.date.available.none.fl_str_mv 2020-05-26T00:07:29Z
dc.type.eng.fl_str_mv article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.spa.spa.fl_str_mv Artículo
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1038/s41431-018-0295-z
dc.identifier.issn.none.fl_str_mv 10184813
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/24006
url https://doi.org/10.1038/s41431-018-0295-z
https://repository.urosario.edu.co/handle/10336/24006
identifier_str_mv 10184813
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.citationEndPage.none.fl_str_mv 962
dc.relation.citationIssue.none.fl_str_mv No. 6
dc.relation.citationStartPage.none.fl_str_mv 952
dc.relation.citationTitle.none.fl_str_mv European Journal of Human Genetics
dc.relation.citationVolume.none.fl_str_mv Vol. 27
dc.relation.ispartof.spa.fl_str_mv European Journal of Human Genetics, ISSN:10184813, Vol.27, No.6 (2019); pp. 952-962
dc.relation.uri.spa.fl_str_mv https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060589966&doi=10.1038%2fs41431-018-0295-z&partnerID=40&md5=bde0cef16de811dba3fa2046484bba2a
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.acceso.spa.fl_str_mv Abierto (Texto Completo)
rights_invalid_str_mv Abierto (Texto Completo)
http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Nature Publishing Group
institution Universidad del Rosario
dc.source.instname.spa.fl_str_mv instname:Universidad del Rosario
dc.source.reponame.spa.fl_str_mv reponame:Repositorio Institucional EdocUR
repository.name.fl_str_mv Repositorio institucional EdocUR
repository.mail.fl_str_mv edocur@urosario.edu.co
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In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits: PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency less than 5%). In addition to many known loci, we identified seven novel locus-trait associations: KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes. © 2019, The Author(s).application/pdfhttps://doi.org/10.1038/s41431-018-0295-z10184813https://repository.urosario.edu.co/handle/10336/24006engNature Publishing Group962No. 6952European Journal of Human GeneticsVol. 27European Journal of Human Genetics, ISSN:10184813, Vol.27, No.6 (2019); pp. 952-962https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060589966&doi=10.1038%2fs41431-018-0295-z&partnerID=40&md5=bde0cef16de811dba3fa2046484bba2aAbierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURAlleleArticleCohort analysisComputer modelDutchmanElectrocardiogramExonFollow upGene frequencyGene locusGene mappingGenomeGenome-wide association studyGenotypeHeart rateHumanMajor clinical studyMeta analysisNetherlandsPriority journalQrs intervalQt intervalQuantitative traitRr intervalSampleSingle nucleotide polymorphismGenome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traitsarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501van Setten, JessicaVerweij, NiekMbarek, HamdiNiemeijer, Maartje N.Trompet, StellaArking, Dan E.Brody, Jennifer A.Gandin, IlariaGrarup, NielsHall, Leanne M.Hemerich, DaianeLyytikäinen, Leo-PekkaMei, HaoMüller-Nurasyid, MartinaPrins, Bram P.Robino, AntoniettaSmith, Albert V.Warren, Helen R.Asselbergs, Folkert W.Boomsma, Dorret I.Caulfield, Mark J.Eijgelsheim, MarkFord, IanHansen, TorbenHarris, Tamara B.Heckbert, Susan R.Hottenga, Jouke-JanIorio, AnnamariaKors, Jan A.Linneberg, AllanMacFarlane, Peter W.Meitinger, ThomasNelson, Christopher P.Raitakari, Olli T.Silva Aldana, Claudia T.Sinagra, GianfrancoSinner, MoritzSoliman, Elsayed Z.Stoll, MonikaUitterlinden, Andrevan Duijn, Cornelia M.Waldenberger, MelanieAlonso, AlvaroGasparini, PaoloGudnason, VilmundurJamshidi, YaldaKääb, StefanKanters, Jørgen K.Lehtimäki, TerhoMunroe, Patricia B.Peters, AnnetteSamani, Nilesh J.Sotoodehnia, NonaUlivi, SheilaWilson, James G.de Geus, Eco J. C.Jukema, J. WouterStricker, Brunovan der Harst, Pimde Bakker, Paul I. W.Isaacs, Aaron10336/24006oai:repository.urosario.edu.co:10336/240062022-05-02 07:37:21.338101https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co