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A prominent clinical and genetic overlap exists between AF, heritable ventricular cardiomyopathies, and arrhythmia syndromes, underlining the potential of AF as an early indicator of severe ventricular disease in younger individuals. Indeed, several recent studies have demonstrated meaningful yields of rare pathogenic variants among early-onset AF patients (\u223c4%\u201311%), most notably for cardiomyopathy genes in which rare variants are considered clinically actionable. Genetic testing thus presents a promising opportunity to identify monogenetic defects linked to AF and inherited cardiac conditions, such as cardiomyopathy, and may contribute to prognosis and management in early-onset AF patients. A first step towards recognizing this monogenic contribution was taken with the Class IIb recommendation for genetic testing in AF patients aged 45 years or younger by the 2023 American College of Cardiology\/American Heart Association guidelines for AF. By identifying pathogenic genetic variants known to underlie inherited cardiomyopathies and arrhythmia syndromes, a personalized care pathway can be developed, encompassing more tailored screening, cascade testing, and potentially genotype-informed prognosis and preventive measures. However, this can only be ensured by frameworks that are developed and supported by all stakeholders. Ambiguity in test results such as variants of uncertain significance remain a major challenge and as many as \u223c60% of people with early-onset AF might carry such variants. Patient education (including pretest counselling), training of genetic teams, selection of high-confidence genes, and careful reporting are strategies to mitigate this. Further challenges to implementation include financial barriers, insurability issues, workforce limitations, and the need for standardized definitions in a fast-moving field. Moreover, the prevailing genetic evidence largely rests on European descent populations, underscoring the need for diverse research cohorts and international collaboration. Embracing these challenges and the potential of genetic testing may improve AF care. However, further research\u2014mechanistic, translational, and clinical\u2014is urgently needed.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehae298","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T16:37:56Z","timestamp":1715272676000},"page":"3111-3123","source":"Crossref","is-referenced-by-count":53,"title":["Genetic testing in early-onset atrial fibrillation"],"prefix":"10.1093","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8113-733X","authenticated-orcid":false,"given":"Shinwan","family":"Kany","sequence":"first","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard , 415 Main St, 02412, Cambridge, MA ,","place":["USA"]},{"name":"Cardiovascular Research Center, Massachusetts General Hospital , 185 Cambridge St, 02114, Boston, MA ,","place":["USA"]},{"name":"Department of Cardiology, University Heart and Vascular Center Hamburg-Eppendorf , Hamburg ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/L\u00fcbeck , Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean J","family":"Jurgens","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard , 415 Main St, 02412, Cambridge, MA ,","place":["USA"]},{"name":"Cardiovascular Research Center, Massachusetts General Hospital , 185 Cambridge St, 02114, Boston, MA ,","place":["USA"]},{"name":"Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias , Amsterdam ,","place":["Netherlands"]},{"name":"Department of Experimental Cardiology, Heart Center, Amsterdam UMC, University of Amsterdam , Meibergdreef 9, Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel T","family":"R\u00e4m\u00f6","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard , 415 Main St, 02412, Cambridge, MA ,","place":["USA"]},{"name":"Cardiovascular Research Center, Massachusetts General Hospital , 185 Cambridge St, 02114, Boston, MA ,","place":["USA"]},{"name":"Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki , Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid E","family":"Christophersen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Baerum Hospital, Vestre Viken Hospital Trust , Rud ,","place":["Norway"]},{"name":"Department of Medical Genetics, Oslo University Hospital , Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2581-070X","authenticated-orcid":false,"given":"Michiel","family":"Rienstra","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina K","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Lerner Research Institute , Cleveland, OH ,","place":["USA"]},{"name":"Department of Cardiovascular Medicine, Cleveland Clinic, Heart, Vascular & Thoracic Institute , Cleveland, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten S","family":"Olesen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8011-3333","authenticated-orcid":false,"given":"Michael J","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Experimental 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9, Amsterdam, the","place":["Netherlands"]},{"name":"European Reference Network for RARE, Low Prevalence and Complex Diseases of the Heart: ERN GUARD-Heart"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4076-2336","authenticated-orcid":false,"given":"Emelia J","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine , Boston, MA ,","place":["USA"]},{"name":"Department of Epidemiology, Boston University School of Public Health , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi L","family":"Rehm","sequence":"additional","affiliation":[{"name":"Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, MA ,","place":["USA"]},{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, MA ,","place":["USA"]},{"name":"Harvard Medical 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