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A combined linkage and exome sequencing analysis for electrocardiogram parameters in the erasmus rucphen family study

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dc.creatorTamar Silva, Claudia
dc.creatorZorkoltseva, Irina V.
dc.creatorAmin, Najaf
dc.creatorDemirkan, Ayse
dc.creatorvan Leeuwen, Elisabeth M.
dc.creatorKors, Jan A.
dc.creatorvan den Berg, Marten
dc.creatorStricker, Bruno H.
dc.creatorUitterlinden, André
dc.creatorKirichenko, Anatoly V.
dc.creatorWitteman, Jacqueline C. M.
dc.creatorWillemsen, Rob
dc.creatorOostra, Ben A.
dc.creatorAxenovich, Tatiana I.
dc.creatorvan Duijn, Cornelia M.
dc.creatorIsaacs, Aaron
dc.creator.googleSilva, Claudia T.spa
dc.creator.googleZorkoltseva, Irina V.spa
dc.creator.googleAmin, Najafspa
dc.creator.googleDemirkan, Aysespa
dc.creator.googlevan Leeuwen, Elisabeth M.spa
dc.creator.googleKors, Jan A.spa
dc.creator.googlevan den Berg, Martenspa
dc.creator.googleStricker, Bruno H.spa
dc.creator.googleUitterlinden, André G.spa
dc.creator.googleKirichenko, Anatoly V.spa
dc.creator.googleWitteman, Jacqueline C. M.spa
dc.creator.googleWillemsen, Robspa
dc.creator.googleOostra, Ben A.spa
dc.creator.googleAxenovich, Tatiana I.spa
dc.creator.googlevan Duijn, Cornelia M.spa
dc.creator.googleIsaacs, Aaronspa
dc.date.accessioned2020-05-12T11:31:52Z
dc.date.available2020-05-12T11:31:52Z
dc.date.created2016
dc.date.issued2016
dc.description.abstractElectrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF). Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2 gene associated with QT (rs74608430; P = 2.8 × 10-4, minor allele frequency = 0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the trait's genetic variability in ERF (P = 0.02). Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3) and AMPK stimulated fatty acid oxidation in muscle (P = 4.1 × 10-3). Look-ups in bioinformatics resources showed that expression of FCRL2 is associated with ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam study. Combining the bioinformatics information with the association and linkage analyses, FCRL2 emerges as a strong candidate gene for QT interval. © 2016 Silva, Zorkoltseva, Amin, Demirkan, van Leeuwen, Kors, van den Berg, Stricker, Uitterlinden, Kirichenko, Witteman, Willemsen, Oostra, Axenovich, van Duijn and Isaacs.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.3389/fgene.2016.00190
dc.identifier.issn1664-8021
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/21979
dc.language.isoengspa
dc.relation.citationIssueNo. NOV
dc.relation.citationTitleFrontiers in Genetics
dc.relation.citationVolumeVol. 7
dc.relation.ispartofFrontiers in Genetics, ISSN: 1664-8021 Vol. 7, No. NOV (2016)spa
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fgene.2016.00190/fullspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subject.ddcPromoción de saludspa
dc.subject.keywordGenetic variabilityspa
dc.subject.keywordHumanspa
dc.subject.keywordGeneticsspa
dc.subject.keywordEpidemiologyspa
dc.subject.keywordElectrocardiographyspa
dc.subject.keywordLinkagespa
dc.subject.keywordExomespa
dc.titleA combined linkage and exome sequencing analysis for electrocardiogram parameters in the erasmus rucphen family studyspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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