{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T23:29:33Z","timestamp":1794266973864,"version":"4.9.0"},"reference-count":35,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"\n Importance<\/jats:title>\n Recurrent pericarditis is a treatment challenge and often a debilitating condition. Drugs inhibiting interleukin 1 cytokines are a promising new treatment option, but their use is based on scarce biological evidence and clinical trials of modest sizes, and the contributions of innate and adaptive immune processes to the pathophysiology are incompletely understood.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To use human genomics, transcriptomics, and proteomics to shed light on the pathogenesis of pericarditis.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This was a meta-analysis of genome-wide association studies of pericarditis from 5 countries. Associations were examined between the pericarditis-associated variants and pericarditis subtypes (including recurrent pericarditis) and secondary phenotypes. To explore mechanisms, associations with messenger RNA expression (\n cis<\/jats:italic>\n -eQTL), plasma protein levels (pQTL), and CpG methylation of DNA (ASM-QTL) were assessed. Data from Iceland (deCODE genetics, 1983-2020), Denmark (Copenhagen Hospital Biobank\/Danish Blood Donor Study, 1977-2022), the UK (UK Biobank, 1953-2021), the US (Intermountain, 1996-2022), and Finland (FinnGen, 1970-2022) were included. Data were analyzed from September 2022 to August 2023.\n <\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Genotype.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Pericarditis.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In this genome-wide association study of 4894 individuals with pericarditis (mean [SD] age at diagnosis, 51.4 [17.9] years, 2734 [67.6%] male, excluding the FinnGen cohort), associations were identified with 2 independent common intergenic variants at the interleukin 1 locus on chromosome 2q14. The lead variant was rs12992780 (T) (effect allele frequency [EAF], 31%-40%; odds ratio [OR], 0.83; 95% CI, 0.79-0.87;\n P<\/jats:italic>\n \u2009=\u20096.67\u2009\u00d7\u200910\n \u221216<\/jats:sup>\n ), downstream of\n IL1B<\/jats:italic>\n and the secondary variant rs7575402 (A or T) (EAF, 45%-55%; adjusted OR, 0.89; 95% CI, 0.85-0.93; adjusted\n P<\/jats:italic>\n \u2009=\u20099.6\u2009\u00d7\u200910\n \u22128<\/jats:sup>\n ). The lead variant rs12992780 had a smaller odds ratio for recurrent pericarditis (0.76) than the acute form (0.86) (\n P<\/jats:italic>\n for heterogeneity\u2009=\u2009.03) and rs7575402 was associated with CpG methylation overlapping binding sites of 4 transcription factors known to regulate interleukin 1 production: PU.1 (encoded by\n SPI1<\/jats:italic>\n ), STAT1, STAT3, and CCAAT\/enhancer-binding protein \u03b2 (encoded by\n CEBPB<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This study found an association between pericarditis and 2 independent sequence variants at the interleukin 1 gene locus. This finding has the potential to contribute to development of more targeted and personalized therapy of pericarditis with interleukin 1\u2013blocking drugs.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2023.4820","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T11:33:05Z","timestamp":1703676785000},"page":"165","source":"Crossref","is-referenced-by-count":35,"title":["Variants at the Interleukin 1 Gene Locus and Pericarditis"],"prefix":"10.1001","volume":"9","author":[{"given":"Rosa B.","family":"Thorolfsdottir","sequence":"first","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea B.","family":"Jonsdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gardar","family":"Sveinbjornsson","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildur M.","family":"Aegisdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmundur","family":"Oddsson","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olafur A.","family":"Stefansson","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisli H.","family":"Halldorsson","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"},{"name":"School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saedis","family":"Saevarsdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"},{"name":"Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland"},{"name":"Department of Medicine, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudmar","family":"Thorleifsson","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilja","family":"Stefansdottir","sequence":"additional","affiliation":[{"name":"deCODE genetics, Amgen, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole B.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Zealand University Hospital, 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Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Erikstrup","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Ullum","sequence":"additional","affiliation":[{"name":"Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Mikkelsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, 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