{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:50:23Z","timestamp":1790214623019,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,7,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional, and arrhythmic disease features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>UK Biobank participants who had undergone whole exome sequencing, ECG, and cardiovascular magnetic resonance imaging were selected for study. Three variant-calling strategies (1 primary and 2 secondary) were used to identify participants with putative pathogenic variants in 44 DCM genes. The observed phenotype was graded DCM (clinical or cardiovascular magnetic resonance diagnosis); early DCM features, including arrhythmia or conduction disease, isolated ventricular dilation, and hypokinetic nondilated cardiomyopathy; or phenotype-negative.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Among 18\u2009665 individuals included in the study, 1463 (7.8%) possessed \u22651 putative pathogenic variant in 44 DCM genes by the main variant calling strategy. A clinical diagnosis of DCM was present in 0.34% and early DCM features in 5.7% of individuals with putative pathogenic variants. ECG and cardiovascular magnetic resonance analysis revealed evidence of subclinical DCM in an additional 1.6% and early DCM features in an additional 15.9% of individuals with putative pathogenic variants. Arrhythmias or conduction disease (15.2%) were the most common early DCM features, followed by hypokinetic nondilated cardiomyopathy (4%). The combined clinical\/subclinical penetrance was \u226430% with all 3 variant filtering strategies. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive\/strong evidence genes as compared with those with variants in moderate\/limited evidence genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In the UK Biobank, \u22481 of 6 of adults with putative pathogenic variants in DCM genes exhibited early DCM features potentially associated with DCM genotype, most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation or dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.121.058143","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T14:00:44Z","timestamp":1657548044000},"page":"110-124","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Frequency, Penetrance, and Variable Expressivity of Dilated Cardiomyopathy\u2013Associated Putative Pathogenic Gene Variants in UK Biobank Participants"],"prefix":"10.1161","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-7706","authenticated-orcid":true,"given":"Ravi A.","family":"Shah","sequence":"first","affiliation":[{"name":"Imperial College Healthcare NHS Trust, London, United Kingdom (R.A.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-5717","authenticated-orcid":true,"given":"Babken","family":"Asatryan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland (B.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7090-1064","authenticated-orcid":true,"given":"Ghaith","family":"Sharaf Dabbagh","sequence":"additional","affiliation":[{"name":"Center for Inherited Cardiovascular Diseases, WellSpan Health, Lancaster, PA (G.S.D., C.A.A.C.)."},{"name":"University of Michigan, Division of Cardiovascular Medicine, Ann Arbor (G.S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nay","family":"Aung","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, St Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, United Kingdom (N.A., M.Y.K., L.R.L., A.M.L., S.E.P., C.A.A.C.)."},{"name":"NIHR Barts Biomedical Research Centre, William Harvey Research Institute, Queen Mary University of London, United Kingdom (N.A., M.Y.K., S.v.D., A.M.L., P.B.M., S.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-4454","authenticated-orcid":true,"given":"Mohammed Y.","family":"Khanji","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, St Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, United Kingdom (N.A., M.Y.K., L.R.L., A.M.L., S.E.P., C.A.A.C.)."},{"name":"NIHR Barts Biomedical Research Centre, William Harvey Research Institute, Queen Mary University of London, United Kingdom (N.A., M.Y.K., S.v.D., A.M.L., P.B.M., S.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6408-4667","authenticated-orcid":true,"given":"Luis R.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, United Kingdom (L.R.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"van Duijvenboden","sequence":"additional","affiliation":[{"name":"NIHR Barts Biomedical Research Centre, William Harvey Research Institute, Queen Mary University of London, United Kingdom (N.A., M.Y.K., S.v.D., A.M.L., P.B.M., S.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Holmes","sequence":"additional","affiliation":[{"name":"GE 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