{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:24:08Z","timestamp":1789547048807,"version":"build-2803163510"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Rare variants in cardiac ion channel genes are associated with sudden cardiac death in rare primary arrhythmic syndromes; however, it is unknown whether common variation in these same genes may contribute to sudden cardiac death risk at the population level.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We examined the association between 147 single nucleotide polymorphisms (SNPs) (137 tag, 5 noncoding SNPs associated with QT interval duration, and 5 nonsynonymous SNPs) in 5 cardiac ion channel genes,\n              <jats:italic>KCNQ1<\/jats:italic>\n              ,\n              <jats:italic>KCNH2<\/jats:italic>\n              ,\n              <jats:italic>SCN5A<\/jats:italic>\n              ,\n              <jats:italic>KCNE1<\/jats:italic>\n              , and\n              <jats:italic>KCNE2<\/jats:italic>\n              , and sudden and\/or arrhythmic death in a combined nested case-control analysis among 516 cases and 1522 matched control subjects of European ancestry enrolled in 6 prospective cohort studies. After accounting for multiple testing, 2 SNPs (rs2283222 located in intron 11 in\n              <jats:italic>KCNQ1<\/jats:italic>\n              and rs11720524 located in intron 1 in\n              <jats:italic>SCN5A<\/jats:italic>\n              ) remained significantly associated with sudden\/arrhythmic death (false discovery rate=0.01 and 0.03, respectively). Each increasing copy of the major T-allele of rs2283222 or the major C-allele of rs1172052 was associated with an odds ratio of 1.36 (95% confidence interval, 1.16 to 1.60;\n              <jats:italic>P<\/jats:italic>\n              =0.0002) and 1.30 (95% confidence interval, 1.12 to 1.51;\n              <jats:italic>P<\/jats:italic>\n              =0.0005), respectively. Control for cardiovascular risk factors and\/or limiting the analysis to definite sudden cardiac death did not significantly alter these relationships.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>\n              In this combined analysis of 6 prospective cohort studies, 2 common intronic variants in\n              <jats:italic>KCNQ1<\/jats:italic>\n              and\n              <jats:italic>SCN5A<\/jats:italic>\n              were associated with sudden cardiac death in individuals of European ancestry. Further study in other populations and investigation into the functional abnormalities associated with noncoding variation in these genes may lead to important insights into predisposition to lethal arrhythmias.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.110.944934","type":"journal-article","created":{"date-parts":[[2010,4,18]],"date-time":"2010-04-18T00:25:27Z","timestamp":1271550327000},"page":"222-229","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Common Variants in Cardiac Ion Channel Genes Are Associated With Sudden Cardiac Death"],"prefix":"10.1161","volume":"3","author":[{"given":"Christine M.","family":"Albert","sequence":"first","affiliation":[{"name":"From the Center for Arrhythmia Prevention (C.M.A.), Division of Preventive Medicine (C.M.A., D.I.C., M.V., J.E.B., J.E.M., N.R.C.), Cardiovascular Division (C.M.A., C.A.M.), Channing Laboratory (J.E.M.), and Division of Aging (J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, (C.N.-C.), Harvard Medical School, Boston, Mass; Program for Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calum A.","family":"MacRae","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Prevention (C.M.A.), Division of Preventive Medicine (C.M.A., D.I.C., M.V., J.E.B., J.E.M., N.R.C.), Cardiovascular Division (C.M.A., C.A.M.), Channing Laboratory (J.E.M.), and Division of Aging (J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, (C.N.-C.), Harvard Medical School, Boston, Mass; Program for Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel I.","family":"Chasman","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Prevention (C.M.A.), Division of Preventive Medicine (C.M.A., D.I.C., M.V., J.E.B., J.E.M., N.R.C.), Cardiovascular Division (C.M.A., C.A.M.), Channing Laboratory (J.E.M.), and Division of Aging (J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, (C.N.-C.), Harvard Medical School, Boston, Mass; Program for Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"VanDenburgh","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Prevention (C.M.A.), Division of Preventive Medicine (C.M.A., D.I.C., M.V., J.E.B., J.E.M., N.R.C.), Cardiovascular Division (C.M.A., C.A.M.), Channing Laboratory (J.E.M.), and Division of Aging (J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, (C.N.-C.), Harvard Medical School, Boston, Mass; Program for Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"Buring","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Prevention (C.M.A.), Division of Preventive Medicine (C.M.A., D.I.C., M.V., J.E.B., J.E.M., N.R.C.), Cardiovascular Division (C.M.A., C.A.M.), Channing Laboratory (J.E.M.), and Division of Aging (J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, (C.N.-C.), Harvard Medical School, Boston, Mass; Program for Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Prevention (C.M.A.), Division of Preventive Medicine (C.M.A., D.I.C., M.V., J.E.B., J.E.M., N.R.C.), Cardiovascular Division (C.M.A., C.A.M.), Channing Laboratory (J.E.M.), and Division of Aging (J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, (C.N.-C.), Harvard Medical School, Boston, Mass; Program for Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy R.","family":"Cook","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Prevention (C.M.A.), Division of Preventive Medicine (C.M.A., D.I.C., M.V., J.E.B., J.E.M., N.R.C.), Cardiovascular Division (C.M.A., C.A.M.), Channing Laboratory (J.E.M.), and Division of Aging (J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, (C.N.-C.), Harvard Medical School, Boston, Mass; Program for Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Newton-Cheh","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Prevention (C.M.A.), Division of Preventive Medicine (C.M.A., D.I.C., M.V., J.E.B., J.E.M., N.R.C.), Cardiovascular Division (C.M.A., C.A.M.), Channing Laboratory (J.E.M.), and Division of Aging (J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; the Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, (C.N.-C.), Harvard Medical School, Boston, Mass; Program for Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc4301.098254"},{"key":"e_1_3_3_3_2","first-page":"I11","article-title":"Long- and short-term risk of sudden coronary death","volume":"85","author":"Cupples LA","year":"1992","unstructured":"Cupples LA, Gagnon DR, Kannel WB. 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