{"doi":"10.1161/jaha.125.041586","title":"<i>CAV1</i>\n                    —A Susceptibility Gene for Atrial Fibrillation: The Impact of Coding and Noncoding Variants","abstract":"<h4>Background</h4>Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with a strong genetic predisposition. Genome-wide association studies have highlighted CAV1 (caveolin 1), a caveolar protein involved in various signaling pathways, as a candidate for cardiac conduction disorders.<h4>Methods</h4>We explored the role of CAV1 in AF in various models to dissect possible disease mechanisms. First, <i>CAV1</i> expression was examined together with the AF risk gene <i>SHOX2</i> in a porcine model of induced AF. Then we screened a cohort of 282 patients with early-onset AF to identify genetic variants within <i>CAV1</i> and found 1 coding and 5 noncoding variants. The coding variant was functionally investigated in zebrafish, and a comprehensive analysis panel was applied to investigate the noncoding variants.<h4>Results</h4>In the porcine AF model, <i>CAV1</i> and <i>SHOX2</i> were significantly downregulated in the right atrium and atrioventricular node. Cardiac-specific overexpression of the coding variant in zebrafish increased heart rate and caused fibrillatory waves and loss of the PR interval, supporting a pathogenic effect. Four of the 5 novel identified noncoding variants showed an association with AF and PR interval in published data sets, including 1 with genome-wide significance. The noncoding variants localized to binding sites of transcription factors EOMES, RFX5, TEAD4 and MAX. Luciferase reporter gene assays demonstrated that 3 variants significantly altered the ability of those transcription factors to activate reporter gene expression.<h4>Conclusions</h4>This work underscores <i>CAV1</i> as an AF susceptibility gene and highlights the critical role of coding and noncoding variants in AF disease mechanisms.","journal":"Journal of the American Heart Association","year":2026,"id":8770,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.039,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2026-02-03","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":75470,"name":"David Rheinert","orcid":"0009-0004-0668-1342","position":1,"is_corresponding":false},{"id":75471,"name":"Annette Löwen","orcid":"0009-0003-4481-6239","position":2,"is_corresponding":false},{"id":75472,"name":"Felix Wiedmann","orcid":"0000-0001-8168-0025","position":3,"is_corresponding":false},{"id":75473,"name":"Sabrina Diebold","orcid":null,"position":4,"is_corresponding":false},{"id":75474,"name":"Federica Diofano","orcid":"0000-0002-7583-2704","position":5,"is_corresponding":false},{"id":75475,"name":"Birgit Weiß","orcid":"0000-0001-6800-4946","position":6,"is_corresponding":false},{"id":75476,"name":"Ralph Röth","orcid":"0000-0002-5032-3348","position":7,"is_corresponding":false},{"id":75477,"name":"Stefanie Schmitteckert","orcid":"0000-0001-9555-2614","position":8,"is_corresponding":false},{"id":75478,"name":"Sebastian Clauss","orcid":"0000-0002-5675-6128","position":9,"is_corresponding":false},{"id":55733,"name":"Stefan Kääb","orcid":"0000-0001-8824-3581","position":10,"is_corresponding":false},{"id":75479,"name":"Steffen Just","orcid":"0000-0001-7396-1281","position":11,"is_corresponding":false},{"id":75480,"name":"Constanze Schmidt","orcid":"0000-0001-5897-237X","position":12,"is_corresponding":false},{"id":75481,"name":"Gudrun A. 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