{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:07:49Z","timestamp":1785276469079,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T00:00:00Z","timestamp":1562112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007687","name":"Svenska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","award":["2008\u201021619"],"award-info":[{"award-number":["2008\u201021619"]}],"id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["521\u20102011\u20102440"],"award-info":[{"award-number":["521\u20102011\u20102440"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["521\u20102014\u20103370"],"award-info":[{"award-number":["521\u20102014\u20103370"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>Carbamazepine (<jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>) causes life\u2010threating T\u2010cell\u2010mediated hypersensitivity reactions, including serious cutaneous adverse reactions (<jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content>s) and drug\u2010induced liver injury (<jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DILI<\/jats:styled-content>). In order to evaluate shared or phenotype\u2010specific genetic predisposing factors for <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content> hypersensitivity reactions, we performed a meta\u2010analysis of two genomewide association studies (<jats:styled-content style=\"fixed-case\">GWAS<\/jats:styled-content>) on a total of 43 well\u2010phenotyped Northern and Southern European <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content> cases and 10,701 population controls and a <jats:styled-content style=\"fixed-case\">GWAS<\/jats:styled-content> on 12 <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DILI<\/jats:styled-content> cases and 8,438 ethnically matched population controls. <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010A*31:01<\/jats:italic> was identified as the strongest genetic predisposing factor for both <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content> (odds ratio (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>)\u00a0=\u00a08.0; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 4.10\u201315.80; <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>1.2\u00a0\u00d7\u00a010<jats:sup>\u22129<\/jats:sup>) and <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DILI<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a07.3; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 2.47\u201323.67; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0004) in European populations. The association with <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010A*31:01<\/jats:italic> in patients with <jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content> was mainly driven by hypersensitivity syndrome (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a012.9; <jats:italic>P<\/jats:italic>\u00a0=\u00a02.1\u00a0\u00d7\u00a010<jats:sup>\u22129<\/jats:sup>) rather than by Stevens\u2010Johnson syndrome\/toxic epidermal necrolysis cases, which showed an association with <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010B*57:01<\/jats:italic>. We also identified a novel risk locus mapping to <jats:italic><jats:styled-content style=\"fixed-case\">ALK<\/jats:styled-content><\/jats:italic> only for <jats:styled-content style=\"fixed-case\">CBZ<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SCAR<\/jats:styled-content> cases, which needs replication in additional cohorts and functional evaluation.<\/jats:p>","DOI":"10.1002\/cpt.1493","type":"journal-article","created":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T01:03:40Z","timestamp":1557277420000},"page":"1028-1036","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Shared Genetic Risk Factors Across Carbamazepine\u2010Induced Hypersensitivity Reactions"],"prefix":"10.1111","volume":"106","author":[{"given":"Paola","family":"Nicoletti","sequence":"first","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Sema4, a Mount Sinai Venture  Stamford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Barrett","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-6735","authenticated-orcid":false,"given":"Laurence","family":"McEvoy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7321-0629","authenticated-orcid":false,"given":"Ann K.","family":"Daly","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guruprasad","family":"Aithal","sequence":"additional","affiliation":[{"name":"National Institute for Health Research (NIHR) Nottingham Biomedical Research Unit Center at the Nottingham University Hospital NHS Trust and University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-4896","authenticated-orcid":false,"given":"M. Isabel","family":"Lucena","sequence":"additional","affiliation":[{"name":"UGC Digestivo Clinical Pharmacology Service Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA) Hospital Universitario Virgen de la Victoria Universidad de M\u00e1laga  M\u00e1laga Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-0757","authenticated-orcid":false,"given":"Raul J.","family":"Andrade","sequence":"additional","affiliation":[{"name":"UGC Digestivo Clinical Pharmacology Service Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA) Hospital Universitario Virgen de la Victoria Universidad de M\u00e1laga  M\u00e1laga Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6368-2622","authenticated-orcid":false,"given":"Mia","family":"Wadelius","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-3280","authenticated-orcid":false,"given":"P\u00e4r","family":"Hallberg","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Stephens","sequence":"additional","affiliation":[{"name":"UGC Digestivo Clinical Pharmacology Service Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA) Hospital Universitario Virgen de la Victoria Universidad de M\u00e1laga  M\u00e1laga Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einar S.","family":"Bjornsson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Landspitali University Hospital  Reykjavik Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Friedmann","sequence":"additional","affiliation":[{"name":"Dermatology Unit School of Medicine University of Southampton  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"Kainu","sequence":"additional","affiliation":[{"name":"Clinical Research Unit for Pulmonary Diseases Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarja","family":"Laitinen","sequence":"additional","affiliation":[{"name":"Clinical Research Unit for Pulmonary Diseases Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Marson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Molokhia","sequence":"additional","affiliation":[{"name":"School of Population Sciences and Health Services Research King's College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Phillips","sequence":"additional","affiliation":[{"name":"Departiment of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Pichler","sequence":"additional","affiliation":[{"name":"ADR\u2010AC GmbH  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Romano","sequence":"additional","affiliation":[{"name":"Allergy Unit Complesso Integrato Columbus  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9151-1145","authenticated-orcid":false,"given":"Neil","family":"Shear","sequence":"additional","affiliation":[{"name":"Sunnybrook Health Sciences Centre University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Sills","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana K.","family":"Tanno","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio Liban\u00eas  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2985-5059","authenticated-orcid":false,"given":"Ashley","family":"Swale","sequence":"additional","affiliation":[{"name":"Department of Systems Biology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris","family":"Floratos","sequence":"additional","affiliation":[{"name":"Department of Systems Biology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Systems Biology Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Target Sciences GSK  King of Prussia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Eshelman School of Pharmacy University of North Carolina Institute for Drug Safety Sciences  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Daly","sequence":"additional","affiliation":[{"name":"Analytic and Translational Genetics Unit Department of Medicine Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"},{"name":"Department of Biostatistics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Alfirevic","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7534-7266","authenticated-orcid":false,"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,3]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.189"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60460-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.113.007450"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03330.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/565320"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/428486a"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004008"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq537"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.08.010"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1013297"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2012.00868.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02533.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1346-8138.2011.01457.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2013.10.003"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1166"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/iji.12017"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2013.40"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.55"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.0278"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1004"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-52"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2016.61"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx400460w"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07873-X"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08158-8"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.379"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00090"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2044"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1375"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.632"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/3406230"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.6.1945"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.12.016"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.06.022"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a001115"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007333200"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.8.12.1661"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.79"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.08.005"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1211"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2010.84"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2307"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2796"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000841"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2013.18"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064683"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.1493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1493","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:27:31Z","timestamp":1699363651000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,3]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1002\/cpt.1493"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1493","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,3]]},"assertion":[{"value":"2019-01-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}