{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:04:32Z","timestamp":1789034672825,"version":"build-2803163510"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs\/AVRT).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP\/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Analyses comprised 2384 AVNRT cases and 106\u2005489 referents, and 2811 AVAP\/AVRT cases and 1,483\u2005093 referents. We identified 2 significant loci for AVNRT, which implicate\n              <jats:italic toggle=\"yes\">NKX2-5<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">TTN<\/jats:italic>\n              as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of\n              <jats:italic toggle=\"yes\">NKX2-5<\/jats:italic>\n              and AVNRT. We identified 3 significant loci for AVAP\/AVRT, which implicate\n              <jats:italic toggle=\"yes\">SCN5A<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">SCN10A<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">TTN\/CCDC141<\/jats:italic>\n              . Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our findings highlight gene regions associated with ion channel function (AVAP\/AVRT), as well as cardiac development and the sarcomere (AVAP\/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.123.004320","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T05:00:39Z","timestamp":1716872439000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1475-4930","authenticated-orcid":true,"given":"Lu-Chen","family":"Weng","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center (L.-C.W.), The Broad Institute of MIT and Harvard, Cambridge."},{"name":"Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge."},{"name":"VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2840-4539","authenticated-orcid":true,"given":"Shaan","family":"Khurshid","sequence":"additional","affiliation":[{"name":"Demoulas Center for Cardiac Arrhythmias (S. Khurshid, P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge."},{"name":"Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7915-0313","authenticated-orcid":true,"given":"Amelia Weber","family":"Hall","sequence":"additional","affiliation":[{"name":"Gene Regulation Observatory (A.W.H.), The Broad Institute of MIT and Harvard, Cambridge."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-299X","authenticated-orcid":true,"given":"Victor","family":"Nauffal","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge."},{"name":"VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women\u2019s Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie N.","family":"Morrill","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan V.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA (Y.V.S.)."},{"name":"VA Atlanta Healthcare System, Decatur, GA (Y.V.S., P.W.F.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-5149","authenticated-orcid":true,"given":"Joel T.","family":"R\u00e4m\u00f6","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge."},{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Finland (J.T.R., A.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Beer","sequence":"additional","affiliation":[{"name":"Heart Institute (D.B., C.M.H.), Geisinger, Danville, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1874-2515","authenticated-orcid":true,"given":"Simon","family":"Lee","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York, NY (S.L., G.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6319-4314","authenticated-orcid":true,"given":"Girish","family":"Nadkarni","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York, NY (S.L., G.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8979-2096","authenticated-orcid":true,"given":"Renee","family":"Johnson","sequence":"additional","affiliation":[{"name":"Victor Chang Cardiac Research Institute (R.J., R.S., D.F.), Darlinghurst, NSW."},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, Australia (R.J., R.S., B.W., D.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4732-4921","authenticated-orcid":true,"given":"Laura","family":"Andreasen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (L.A., J.P.H., J.H.S., M.S.O.)."},{"name":"Department of Biomedical Sciences (L.A., M.S.O.), University of Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2884-9062","authenticated-orcid":true,"given":"Anne","family":"Clayton","sequence":"additional","affiliation":[{"name":"Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (A.C., H.T.M., S. 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