dc.date.accessioned | 2021-03-25T20:19:26Z | |
dc.date.available | 2021-03-25T20:19:26Z | |
dc.date.created | 2021-02-12T12:07:24Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Vad, Oliver Bundgaard Paludan-Müller, Chrirstian Ahlberg, Gustav Kalstø, Silje Madeleine Ghouse, Jonas Andreasen, Laura Haunsø, Stig Tveit, Arnljot Sajadieh, Ahmad Christophersen, Ingrid E. Svendsen, Jesper Hastrup Olesen, Morten Salling . Loss-of-Function Variants in Cytoskeletal Genes Are Associated with Early-Onset Atrial Fibrillation. Journal of Clinical Medicine. 2020 | |
dc.identifier.uri | http://hdl.handle.net/10852/84820 | |
dc.description.abstract | Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with an increased risk of heart failure, stroke, dementia, and death. Recently, titin-truncating variants (TTNtv), which are predominantly associated with dilated cardiomyopathy (DCM), were associated with early-onset AF. Furthermore, genome-wide association studies (GWAS) associated AF with other structural genes. In this study, we investigated whether early-onset AF was associated with loss-of-function variants in DCM-associated genes encoding cytoskeletal proteins. Using targeted sequencing, we examined a cohort of 527 Scandinavian individuals with early-onset AF and a control group of individuals free of AF (n = 383). The patients had onset of AF before 50 years of age, normal echocardiogram, and no other cardiovascular disease at onset of AF. We identified six individuals with rare loss-of-function variants in three different genes (dystrophin (DMD), actin-associated LIM protein (PDLIM3), and fukutin (FKTN)), of which two variants were novel. Loss-of-function variants in cytoskeletal genes were significantly associated with early-onset AF when patients were compared with controls (p = 0.044). Using publicly available GWAS data, we performed genetic correlation analyses between AF and 13 other traits, e.g., showing genetic correlation between AF and non-ischemic cardiomyopathy (p = 0.0003). Our data suggest that rare loss-of-function variants in cytoskeletal genes previously associated with DCM may have a role in early-onset AF, perhaps through the development of an atrial cardiomyopathy. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Loss-of-Function Variants in Cytoskeletal Genes Are Associated with Early-Onset Atrial Fibrillation | |
dc.type | Journal article | |
dc.creator.author | Vad, Oliver Bundgaard | |
dc.creator.author | Paludan-Müller, Chrirstian | |
dc.creator.author | Ahlberg, Gustav | |
dc.creator.author | Kalstø, Silje Madeleine | |
dc.creator.author | Ghouse, Jonas | |
dc.creator.author | Andreasen, Laura | |
dc.creator.author | Haunsø, Stig | |
dc.creator.author | Tveit, Arnljot | |
dc.creator.author | Sajadieh, Ahmad | |
dc.creator.author | Christophersen, Ingrid E. | |
dc.creator.author | Svendsen, Jesper Hastrup | |
dc.creator.author | Olesen, Morten Salling | |
cristin.unitcode | 185,53,11,10 | |
cristin.unitname | Hjertemedisinsk avdeling | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1889154 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal of Clinical Medicine&rft.volume=&rft.spage=&rft.date=2020 | |
dc.identifier.jtitle | Journal of Clinical Medicine | |
dc.identifier.volume | 9 | |
dc.identifier.issue | 2 | |
dc.identifier.doi | https://doi.org/10.3390/jcm9020372 | |
dc.identifier.urn | URN:NBN:no-87587 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2077-0383 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/84820/2/Vad%2Bet%2Bal.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 372 | |
dc.relation.project | NFR/240149 | |
dc.relation.project | NOVO/NNF17OC0031204) | |
dc.relation.project | NOVO/NNF18OC0053094 | |