{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:51:31Z","timestamp":1781189491917,"version":"3.54.1"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF18OC0053094"],"award-info":[{"award-number":["NNF18OC0053094"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF17OC0031204"],"award-info":[{"award-number":["NNF17OC0031204"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The John and Birthe Meyer foundation","award":["-"],"award-info":[{"award-number":["-"]}]},{"DOI":"10.13039\/501100009925","name":"Villadsen family foundation","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100009925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Arvid Nilsson Foundation","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Fondsb\u00f8rsvekselerer Henry Hansen og Hustru Karla Hansen, f\u00f8dt Westergaards Legat","award":["-"],"award-info":[{"award-number":["-"]}]},{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"name":"South-Eastern Norway Health Authority","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/jcm9020372","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T10:51:07Z","timestamp":1580295067000},"page":"372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Loss-of-Function Variants in Cytoskeletal Genes Are Associated with Early-Onset Atrial Fibrillation"],"prefix":"10.3390","volume":"9","author":[{"given":"Oliver Bundgaard","family":"Vad","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"},{"name":"Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen O, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Paludan-M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"},{"name":"Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen O, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustav","family":"Ahlberg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"},{"name":"Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen O, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silje Madeleine","family":"Kalst\u00f8","sequence":"additional","affiliation":[{"name":"Department of Medical Research, B\u00e6rum Hospital, Vestre Viken Hospital Trust, 3004 Drammen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Ghouse","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"},{"name":"Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen O, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4732-4921","authenticated-orcid":false,"given":"Laura","family":"Andreasen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"},{"name":"Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen O, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stig","family":"Hauns\u00f8","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen O, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnljot","family":"Tveit","sequence":"additional","affiliation":[{"name":"Department of Medical Research, B\u00e6rum Hospital, Vestre Viken Hospital Trust, 3004 Drammen, Norway"},{"name":"Department of Cardiology, Institute of Clinical Medicine, University of Oslo, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Sajadieh","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital, Bispebjerg, 2400 Copenhagen NV, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid Elisabeth","family":"Christophersen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, B\u00e6rum Hospital, Vestre Viken Hospital Trust, 3004 Drammen, Norway"},{"name":"Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-8515","authenticated-orcid":false,"given":"Jesper Hastrup","family":"Svendsen","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen O, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Salling","family":"Olesen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"},{"name":"Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen O, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/CIRCULATIONAHA.113.005119","article-title":"Worldwide epidemiology of atrial fibrillation: A Global Burden of Disease 2010 Study","volume":"129","author":"Chugh","year":"2014","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1093\/eurheartj\/ehw210","article-title":"2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS","volume":"37","author":"Kirchhof","year":"2016","journal-title":"Eur. 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