{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:41:07Z","timestamp":1771047667114,"version":"3.50.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,7,18]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Long\u2010QT syndrome (LQTS) is a cardiac repolarization abnormality that can lead to sudden cardiac death. The most common causes are rare coding variants in the genes\n              <jats:italic>KCNQ1<\/jats:italic>\n              ,\n              <jats:italic>KCNH2<\/jats:italic>\n              , and\n              <jats:italic>SCN5A<\/jats:italic>\n              . The data on LQTS epidemiology are limited, and information on expressivity and penetrance of pathogenic variants is sparse.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We screened for rare coding variants associated with the corrected QT (QTc) interval in Iceland. We explored the frequency of the identified variants, their penetrance, and their association with severe events. Twelve variants were associated with the QTc interval. Five in\n              <jats:italic>KCNQ<\/jats:italic>\n              1, 3 in\n              <jats:italic>KCNH2<\/jats:italic>\n              , 2 in cardiomyopathy genes\n              <jats:italic>MYBPC3<\/jats:italic>\n              and\n              <jats:italic>PKP2<\/jats:italic>\n              , and 2 in genes where coding variants have not been associated with the QTc interval,\n              <jats:italic>ISOC1<\/jats:italic>\n              and\n              <jats:italic>MYOM2.<\/jats:italic>\n              The combined carrier frequency of the 8 variants in the previously known LQTS genes was 530 per 100\u2009000 individuals (1:190). p.Tyr315Cys and p.Leu273Phe in\n              <jats:italic>KCNQ1<\/jats:italic>\n              were associated with having a mean QTc interval longer than 500\u2009ms (\n              <jats:italic>P<\/jats:italic>\n              =4.2\u00d710\n              <jats:sup>\u22127<\/jats:sup>\n              ; odds ratio [OR], 38.6;\n              <jats:italic>P<\/jats:italic>\n              =8.4\u00d710\n              <jats:sup>\u221210<\/jats:sup>\n              , OR, 26.5; respectively), and p.Leu273Phe was associated with sudden cardiac death (\n              <jats:italic>P<\/jats:italic>\n              =0.0034; OR, 2.99). p.Val215Met in\n              <jats:italic>KCNQ1<\/jats:italic>\n              was carried by 1 in 280 Icelanders, had a smaller effect on the QTc interval (\n              <jats:italic>P<\/jats:italic>\n              =1.8\u00d710\n              <jats:sup>\u221244<\/jats:sup>\n              ; effect, 22.8\u2009ms), and did not associate with severe clinical events.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The carrier frequency of associating variants in LQTS genes was higher than previous estimates of the prevalence of LQTS. The variants have variable effects on the QTc interval, and carriers of p.Tyr315Cys and p.Leu273Phe have a more severe disease than carriers of p.Val215Met. These data could lead to improved identification, risk stratification, and a more precise clinical approach to those with QTc prolongation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.029845","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T10:59:58Z","timestamp":1689332398000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Screening for Rare Coding Variants That Associate With the QTc Interval in Iceland"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2429-9468","authenticated-orcid":false,"given":"Gardar","family":"Sveinbjornsson","sequence":"first","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bara D.","family":"Benediktsdottir","sequence":"additional","affiliation":[{"name":"Internal Medicine, Landspitali\u2013The National University Hospital of Iceland Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnlaugur","family":"Sigfusson","sequence":"additional","affiliation":[{"name":"Children\u2019s Medical Center Landsp\u00edtali\u2013The National University Hospital of Iceland Reykjav\u00edk Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristjan","family":"Norland","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7226-5409","authenticated-orcid":false,"given":"Olafur B.","family":"Davidsson","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa B.","family":"Thorolfsdottir","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8223-8957","authenticated-orcid":false,"given":"Vinicius","family":"Tragante","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-423X","authenticated-orcid":false,"given":"Gudny A.","family":"Arnadottir","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brynjar O.","family":"Jensson","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hildigunnur","family":"Katrinardottir","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Run","family":"Fridriksdottir","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hallbera","family":"Gudmundsdottir","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hildur M.","family":"Aegisdottir","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brynjar","family":"Fridriksson","sequence":"additional","affiliation":[{"name":"The Capital District Fire and Rescue Service Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7146-1395","authenticated-orcid":false,"given":"Gudmundur","family":"Thorgeirsson","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidar","family":"Magnusson","sequence":"additional","affiliation":[{"name":"The Capital District Fire and Rescue Service Reykjavik Iceland"},{"name":"Department of Anesthesia, Landspitali The National University Hospital of Iceland Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4606-5163","authenticated-orcid":false,"given":"Asmundur","family":"Oddsson","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-6123","authenticated-orcid":false,"given":"Patrick","family":"Sulem","sequence":"additional","affiliation":[{"name":"deCODE Genetics\/Amgen, Inc. 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