{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:57:34Z","timestamp":1793141854411,"version":"4.5.0"},"reference-count":47,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2021,12,1]]},"DOI":"10.1001\/jamacardio.2021.3370","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T11:14:00Z","timestamp":1631099640000},"page":"1371","source":"Crossref","is-referenced-by-count":195,"title":["Early-Onset Atrial Fibrillation and the Prevalence of Rare Variants in Cardiomyopathy and Arrhythmia Genes"],"prefix":"10.1001","volume":"6","author":[{"given":"Zachary T.","family":"Yoneda","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine C.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Quintana","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Sims","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Glazer","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Stricker","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinn","family":"Wells","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne W.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory F.","family":"Michaud","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawood","family":"Darbar","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Illinois at Chicago, Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Lubitz","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts"},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick T.","family":"Ellinor","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts"},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan M.","family":"Roden","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Benjamin","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"8","key":"hoi210059r1","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1016\/j.hrthm.2011.05.020","article-title":"HRS\/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).","volume":"8","author":"Ackerman","year":"2011","journal-title":"Heart Rhythm"},{"issue":"23","key":"hoi210059r2","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1161\/CIR.0000000000000040","article-title":"2014 AHA\/ACC\/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology\/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society.","volume":"130","author":"January","year":"2014","journal-title":"Circulation"},{"issue":"3","key":"hoi210059r3","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.jacep.2020.11.006","article-title":"Genetic testing for early onset atrial arrhythmias changes clinical management: 2 cases of cardiac emerinopathy.","volume":"7","author":"Yoneda","year":"2021","journal-title":"JACC Clin Electrophysiol"},{"issue":"11","key":"hoi210059r4","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCGEN.119.002713","article-title":"Broad genetic testing in a clinical setting uncovers a high prevalence of titin loss-of-function variants in very early onset atrial fibrillation.","volume":"12","author":"Goodyer","year":"2019","journal-title":"Circ Genom Precis Med"},{"issue":"22","key":"hoi210059r5","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1001\/jama.2018.18179","article-title":"Association between titin loss-of-function variants and early-onset atrial fibrillation.","volume":"320","author":"Choi","year":"2018","journal-title":"JAMA"},{"issue":"2","key":"hoi210059r6","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.hrthm.2013.10.034","article-title":"Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation.","volume":"11","author":"Olesen","year":"2014","journal-title":"Heart Rhythm"},{"issue":"6","key":"hoi210059r7","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1093\/europace\/euaa421","article-title":"Enrichment of loss-of-function and copy number variants in ventricular cardiomyopathy genes in \u2018lone\u2019 atrial fibrillation.","volume":"23","author":"Lazarte","year":"2021","journal-title":"Europace"},{"issue":"5604","key":"hoi210059r8","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1126\/science.1077771","article-title":"KCNQ1 gain-of-function mutation in familial atrial fibrillation.","volume":"299","author":"Chen","year":"2003","journal-title":"Science"},{"issue":"7","key":"hoi210059r9","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1093\/eurheartj\/ehm619","article-title":"The non-synonymous coding IKr-channel variant KCNH2-K897T is associated with atrial fibrillation: results from a systematic candidate gene-based analysis of KCNH2 (HERG).","volume":"29","author":"Sinner","year":"2008","journal-title":"Eur Heart J"},{"issue":"4","key":"hoi210059r10","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1001\/jama.293.4.447","article-title":"Sodium channel mutations and susceptibility to heart failure and atrial fibrillation.","volume":"293","author":"Olson","year":"2005","journal-title":"JAMA"},{"issue":"5","key":"hoi210059r11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1161\/CIRCULATIONAHA.119.037661","article-title":"Reevaluating the genetic contribution of monogenic dilated cardiomyopathy.","volume":"141","author":"Mazzarotto","year":"2020","journal-title":"Circulation"},{"issue":"364","key":"hoi210059r12","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aag2367","article-title":"Aggregate penetrance of genomic variants for actionable disorders in European and African Americans.","volume":"8","author":"Natarajan","year":"2016","journal-title":"Sci Transl Med"},{"issue":"3","key":"hoi210059r13","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1101\/gr.183483.114","article-title":"Actionable exomic incidental findings in 6503 participants: challenges of variant classification.","volume":"25","author":"Amendola","year":"2015","journal-title":"Genome Res"},{"issue":"1","key":"hoi210059r14","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s00439-017-1852-1","article-title":"Actionable secondary findings from whole-genome sequencing of 954 East Asians.","volume":"137","author":"Tang","year":"2018","journal-title":"Hum Genet"},{"issue":"4","key":"hoi210059r15","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1007\/s00438-018-1431-8","article-title":"Incidental and clinically actionable genetic variants in 1005 whole exomes and genomes from Qatar.","volume":"293","author":"Jain","year":"2018","journal-title":"Mol Genet Genomics"},{"issue":"7831","key":"hoi210059r16","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41586-020-2853-0","article-title":"Exome sequencing and characterization of 49,960 individuals in the UK Biobank.","volume":"586","author":"Van Hout","year":"2020","journal-title":"Nature"},{"issue":"9","key":"hoi210059r17","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1038\/s41436-020-0810-9","article-title":"Frequency of genomic secondary findings among 21,915 eMERGE network participants.","volume":"22","author":"eMERGE Clinical Annotation Working Group","year":"2020","journal-title":"Genet Med"},{"issue":"1","key":"hoi210059r18","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1161\/CIRCRESAHA.120.316365","article-title":"How will genetics inform the clinical care of atrial fibrillation?","volume":"127","author":"Shoemaker","year":"2020","journal-title":"Circ Res"},{"issue":"23","key":"hoi210059r19","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1056\/NEJMsr1406261","article-title":"ClinGen: the clinical genome resource.","volume":"372","author":"Rehm","year":"2015","journal-title":"N Engl J Med"},{"issue":"1","key":"hoi210059r20","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13073-019-0702-2","article-title":"Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases.","volume":"11","author":"Salfati","year":"2019","journal-title":"Genome Med"},{"issue":"5","key":"hoi210059r21","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"8","key":"hoi210059r22","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1093\/hmg\/ddu733","article-title":"Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies.","volume":"24","author":"Dong","year":"2015","journal-title":"Hum Mol Genet"},{"issue":"11","key":"hoi210059r23","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1002\/humu.2018.39.issue-11","article-title":"ClinGen Variant Curation Expert Panel experiences and standardized processes for disease and gene-level specification of the ACMG\/AMP guidelines for sequence variant interpretation.","volume":"39","author":"Rivera-Mu\u00f1oz","year":"2018","journal-title":"Hum Mutat"},{"issue":"11","key":"hoi210059r24","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1002\/humu.2018.39.issue-11","article-title":"Recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion.","volume":"39","author":"Abou Tayoun","year":"2018","journal-title":"Hum Mutat"},{"issue":"11","key":"hoi210059r25","doi-asserted-by":"publisher","first-page":"e373","DOI":"10.1016\/j.hrthm.2019.09.019","article-title":"2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: executive summary.","volume":"16","author":"Towbin","year":"2019","journal-title":"Heart Rhythm"},{"issue":"12","key":"hoi210059r26","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1016\/j.hrthm.2013.05.014","article-title":"HRS\/EHRA\/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.","volume":"10","author":"Priori","year":"2013","journal-title":"Heart Rhythm"},{"issue":"2","key":"hoi210059r27","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/jce.v31.2","article-title":"Epidemiology and clinical characteristics of atrial fibrillation in patients with inherited heart diseases.","volume":"31","author":"Butters","year":"2020","journal-title":"J Cardiovasc Electrophysiol"},{"issue":"1","key":"hoi210059r28","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.1016\/j.hrthm.2016.05.028","article-title":"EHRA\/HRS\/APHRS\/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.","volume":"14","author":"Goette","year":"2017","journal-title":"Heart Rhythm"},{"issue":"2","key":"hoi210059r29","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1161\/CIRCRESAHA.119.315686","article-title":"Monogenic and polygenic contributions to atrial fibrillation risk: results from a national biobank.","volume":"126","author":"Choi","year":"2020","journal-title":"Circ Res"},{"issue":"4","key":"hoi210059r30","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/ng.781","article-title":"A rare variant in MYH6 is associated with high risk of sick sinus syndrome.","volume":"43","author":"Holm","year":"2011","journal-title":"Nat Genet"},{"issue":"17","key":"hoi210059r31","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1016\/j.jacc.2017.09.005","article-title":"A missense variant in PLEC increases risk of atrial fibrillation.","volume":"70","author":"Thorolfsdottir","year":"2017","journal-title":"J Am Coll Cardiol"},{"issue":"23","key":"hoi210059r32","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1056\/NEJM199912023412302","article-title":"Missense mutations in the rod domain of the lamin A\/C gene as causes of dilated cardiomyopathy and conduction-system disease.","volume":"341","author":"Fatkin","year":"1999","journal-title":"N Engl J Med"},{"issue":"5","key":"hoi210059r33","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.hrthm.2009.01.037","article-title":"A novel mutation in LAMIN A\/C is associated with isolated early-onset atrial fibrillation and progressive atrioventricular block followed by cardiomyopathy and sudden cardiac death.","volume":"6","author":"Pan","year":"2009","journal-title":"Heart Rhythm"},{"issue":"1","key":"hoi210059r34","doi-asserted-by":"publisher","first-page":"4093","DOI":"10.1038\/s41598-019-39911-x","article-title":"Relevance of titin missense and non-frameshifting insertions\/deletions variants in dilated cardiomyopathy.","volume":"9","author":"Akinrinade","year":"2019","journal-title":"Sci Rep"},{"issue":"2","key":"hoi210059r35","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/ng.516","article-title":"Genetic variation in SCN10A influences cardiac conduction.","volume":"42","author":"Chambers","year":"2010","journal-title":"Nat Genet"},{"issue":"2","key":"hoi210059r36","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/ng.517","article-title":"Genome-wide association study of PR interval.","volume":"42","author":"Pfeufer","year":"2010","journal-title":"Nat Genet"},{"issue":"12","key":"hoi210059r37","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1038\/ng.716","article-title":"Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.","volume":"42","author":"Sotoodehnia","year":"2010","journal-title":"Nat Genet"},{"issue":"2","key":"hoi210059r38","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/ng.511","article-title":"Several common variants modulate heart rate, PR interval and QRS duration.","volume":"42","author":"Holm","year":"2010","journal-title":"Nat Genet"},{"issue":"5","key":"hoi210059r39","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCGEN.116.001663","article-title":"Common coding variants in SCN10A are associated with the Nav1.8 late current and cardiac conduction.","volume":"11","author":"Macri","year":"2018","journal-title":"Circ Genom Precis Med"},{"issue":"4","key":"hoi210059r40","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1172\/JCI73140","article-title":"A common genetic variant within SCN10A modulates cardiac SCN5A expression.","volume":"124","author":"van den Boogaard","year":"2014","journal-title":"J Clin Invest"},{"issue":"7","key":"hoi210059r41","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1172\/JCI62613","article-title":"Genetic variation in T-box binding element functionally affects SCN5A\/SCN10A enhancer.","volume":"122","author":"van den Boogaard","year":"2012","journal-title":"J Clin Invest"},{"issue":"2","key":"hoi210059r42","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1161\/01.CIR.103.2.196","article-title":"Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia.","volume":"103","author":"Priori","year":"2001","journal-title":"Circulation"},{"issue":"1","key":"hoi210059r43","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1161\/01.CIR.0000020013.73106.D8","article-title":"Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia.","volume":"106","author":"Priori","year":"2002","journal-title":"Circulation"},{"issue":"22","key":"hoi210059r44","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.1016\/j.jacc.2016.09.927","article-title":"Truncating FLNC mutations are associated with high-risk dilated and arrhythmogenic cardiomyopathies.","volume":"68","author":"Ortiz-Genga","year":"2016","journal-title":"J Am Coll Cardiol"},{"issue":"11","key":"hoi210059r45","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.4065\/79.11.1380","article-title":"Targeted mutational analysis of the RyR2-encoded cardiac ryanodine receptor in sudden unexplained death: a molecular autopsy of 49 medical examiner\/coroner\u2019s cases.","volume":"79","author":"Tester","year":"2004","journal-title":"Mayo Clin Proc"},{"issue":"1","key":"hoi210059r46","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1001\/jama.2015.17701","article-title":"Association of arrhythmia-related genetic variants with phenotypes documented in electronic medical records.","volume":"315","author":"Van Driest","year":"2016","journal-title":"JAMA"},{"issue":"7","key":"hoi210059r47","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1001\/jamacardio.2021.0994","article-title":"Association of rare genetic variants and early-onset atrial fibrillation in ethnic minority individuals.","volume":"6","author":"Chalazan","year":"2021","journal-title":"JAMA Cardiol"}],"container-title":["JAMA Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/articlepdf\/2783693\/jamacardiology_yoneda_2021_oi_210059_1637772536.16383.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T11:02:53Z","timestamp":1639393373000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/fullarticle\/2783693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,1]]},"references-count":47,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamacardio.2021.3370","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.740774225.793588576","asserted-by":"object"}]},"ISSN":["2380-6583"],"issn-type":[{"value":"2380-6583","type":"print"}],"subject":[],"published":{"date-parts":[[2021,12,1]]}}}