{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:24:27Z","timestamp":1793121867797,"version":"4.5.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"\n Importance<\/jats:title>\n Rare monogenic variants linked to nonischemic dilated cardiomyopathy (DCM) are enriched among individuals with secondary cardiomyopathies, such as peripartum (PPCM), alcohol-induced (ACM), and cancer therapy\u2013related (CCM) cardiomyopathies. However, it remains unclear whether a polygenic predisposition to DCM also contributes to these conditions.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the association of a DCM polygenic score with PPCM, ACM, and CCM, and to evaluate the contributions of monogenic and polygenic susceptibilities to these secondary cardiomyopathies.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a retrospective genetic association analysis of data from the Mass General Brigham (MGB) Biobank (n\u2009=\u200942\u202f137, 2008-2025), with replication in the UK Biobank (n\u2009=\u2009295\u202f160, 2005-2010), FinnGen (n\u2009=\u2009417\u202f950, 2017-2025), and the Veterans Affairs Million Veteran Program (n\u2009=\u2009516\u202f066, 2011-2025). In MGB Biobank, medical records were reviewed to ascertain secondary cardiomyopathy cases and antecedent clinical risk factors.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n DCM polygenic risk score and DCM monogenic variants.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcomes were the association of the DCM polygenic risk score with PPCM, ACM, and CCM and the prevalence of monogenic variants and a high polygenic score among individuals with cardiomyopathy.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The mean (SD) age in the MGB Biobank was 55.7 (17.0) years at enrollment, and 24\u202f551 (58.3%) were female. Across the 4 study cohorts, 3414 individuals with secondary cardiomyopathy were identified, including 70 with PPCM, 2281 with ACM, and 1063 with CCM. The DCM polygenic score was associated with PPCM (odds ratio [OR], 1.82 per SD; 95% CI, 1.43-2.30), ACM (OR, 1.56; 95% CI,1.34-1.82), and CCM (OR, 1.64; 95% CI,1.24-2.15) (all with\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Monogenic variants were enriched but present in 7 of 113 individuals with medical record\u2013reviewed cardiomyopathy in MGB, while 66 had a high polygenic score, which conferred an approximately 3-fold increased odds of cardiomyopathy. Most individuals with cardiomyopathy lacked antecedent clinical risk factors.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study, individuals with PPCM, ACM, and CCM were enriched for monogenic DCM variants and a high DCM polygenic score, suggesting a shared genetic susceptibility influenced by distinct environmental precipitants. These findings support a shared genetic architecture between secondary cardiomyopathies and DCM, although additional work with larger numbers of individuals with cardiomyopathy is needed to confirm these findings.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2025.3248","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:00:44Z","timestamp":1759330844000},"page":"1138","source":"Crossref","is-referenced-by-count":9,"title":["Polygenic Susceptibility in Peripartum, Alcohol-Induced, and Cancer Therapy\u2013Related Cardiomyopathies"],"prefix":"10.1001","volume":"10","author":[{"given":"Dimitri J.","family":"Maamari","sequence":"first","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts"},{"name":"Department of Medicine, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran J.","family":"Biddinger","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts"},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston"},{"name":"Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston"},{"name":"Department of Operations Research and Financial Engineering, Princeton University, Princeton, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean J.","family":"Jurgens","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts"},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston"},{"name":"Department of Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center Location University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel T.","family":"R\u00e4m\u00f6","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts"},{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Gaziano","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts"},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Zheng","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts"},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston"},{"name":"Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saketh P.","family":"Challa","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolphurs","family":"Hayes","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Gongora","sequence":"additional","affiliation":[{"name":"Cardiology Division, Montefiore Healthcare Network\/Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hoan","family":"Choi","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyong-Mi","family":"Chang","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania"},{"name":"Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Tsao","sequence":"additional","affiliation":[{"name":"Palo Alto Veterans Institute for Research, Palo Alto Health Care System, Palo Alto, California"},{"name":"Department of Medicine and Cardiovascular Institute, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Arany","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paaladinesh","family":"Thavendiranathan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Ted Rogers Program in 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