Variants at the Interleukin 1 Gene Locus and Pericarditis Article Swipe

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Rósa B. Þórólfsdóttir , Andrea B. Jonsdottir , Garðar Sveinbjörnsson , Hildur M. Aegisdottir , Ásmundur Oddsson , Ólafur Andri Stefánsson , Gísli H. Halldórsson , Saedís Saevarsdóttir , Guðmar Þorleifsson , Lilja Stefánsdóttir , Ole Birger Pedersen , Erik Sørensen , Jonas Ghouse , Anna Axelsson Raja , Chaoqun Zheng , Elvira Silajdzija , Søren A Rand , Christian Erikstrup , Henrik Ullum , Christina Mikkelsen , Karina Banasik , Søren Brunak , Erna V. Ivarsdottir , Ásgeir Sigurðsson , Doruk Beyter , Árni Sturluson , Hafsteinn Einarsson , Vinicius Tragante , Hannes Helgason , Sigrún H. Lund , Bjarni V. Halldórsson , Brynja D. Sigurpalsdottir , Ísleifur Ólafsson , Davíð O. Arnar , Guðmundur Þorgeirsson , Kirk U. Knowlton , Lincoln Nadauld , Sólveig Grétarsdóttir , Anna Helgadóttir , Sisse Rye Ostrowski , Daniel F. Gudbjartssson , Ingileif Jónsdóttir , Henning Bundgaard , Hilma Hólm , Patrick Sulem , Kāri Stefánsson , Karina Banasik , Jakob Thaning Bay , Jens Kjærgaard Boldsen , Thorsten Brodersen , Søren Brunak , Kristoffer Sølvsten Burgdorf , Mona Ameri Chalmer , Maria Didriksen , Khoa Manh Dinh , Joseph Dowsett , Christian Erikstrup , Bjarke Feenstra , Frank Geller , Daníel F. Guðbjartsson , Thomas Folkmann Hansen , Lotte Hindhede , Henrik Hjalgrim , Rikke Louise Jacobsen , Gregor B. E. Jemec , Bitten Aagaard Jensen , Kathrine Agergård Kaspersen , Bertram Kjerulff , Lisette J. A. Kogelman , Margit Anita Hørup Larsen , Ioannis Louloudis , Agnete Troen Lundgaard , Christina Mikkelsen , Christina Mikkelsen , Janna Nissen , Mette Nyegaard , Sisse Rye Ostrowski , Ole Birger Pedersen , Alexander Pil Henriksen , Palle Duun Rohde , Klaus Rostgaard , Michael Schwinn , Hreinn Stefánsson , Hreinn Stefánsson , Erik Sørensen , Unnur Þorsteinsdóttir , Lise Wegner Thørner , Mie Topholm Bruun , Henrik Ullum , Thomas Werge , David Westergaard ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1001/jamacardio.2023.4820

Importance 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. Objective To use human genomics, transcriptomics, and proteomics to shed light on the pathogenesis of pericarditis. Design, Setting, and Participants 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 ( cis -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. Exposure Genotype. Main Outcomes and Measures Pericarditis. Results 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; P = 6.67 × 10 −16 ), downstream of IL1B and the secondary variant rs7575402 (A or T) (EAF, 45%-55%; adjusted OR, 0.89; 95% CI, 0.85-0.93; adjusted P = 9.6 × 10 −8 ). The lead variant rs12992780 had a smaller odds ratio for recurrent pericarditis (0.76) than the acute form (0.86) ( P for heterogeneity = .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 SPI1 ), STAT1, STAT3, and CCAAT/enhancer-binding protein β (encoded by CEBPB ). Conclusions and Relevance 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–blocking drugs.

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Medicine Locus (genetics) Gene Genetics Interleukin Pericarditis Immunology Internal medicine Cytokine Biology

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Type: letter
Language: en
Landing Page: https://doi.org/10.1001/jamacardio.2023.4820
OA Status: green
Cited By: 21
References: 36
Related Works: 10
OpenAlex ID: https://openalex.org/W4390275334

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DOI: https://doi.org/10.1001/jamacardio.2023.4820

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Title: Variants at the Interleukin 1 Gene Locus and Pericarditis

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Publication year: 2023

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Authors: Rósa B. Þórólfsdóttir, Andrea B. Jonsdottir, Garðar Sveinbjörnsson, Hildur M. Aegisdottir, Ásmundur Oddsson, Ólafur Andri Stefánsson, Gísli H. Halldórsson, Saedís Saevarsdóttir, Guðmar Þorleifsson, Lilja Stefánsdóttir, Ole Birger Pedersen, Erik Sørensen, Jonas Ghouse, Anna Axelsson Raja, Chaoqun Zheng, Elvira Silajdzija, Søren A Rand, Christian Erikstrup, Henrik Ullum, Christina Mikkelsen, Karina Banasik, Søren Brunak, Erna V. Ivarsdottir, Ásgeir Sigurðsson, Doruk Beyter, Árni Sturluson, Hafsteinn Einarsson, Vinicius Tragante, Hannes Helgason, Sigrún H. Lund, Bjarni V. Halldórsson, Brynja D. Sigurpalsdottir, Ísleifur Ólafsson, Davíð O. Arnar, Guðmundur Þorgeirsson, Kirk U. Knowlton, Lincoln Nadauld, Sólveig Grétarsdóttir, Anna Helgadóttir, Sisse Rye Ostrowski, Daniel F. Gudbjartssson, Ingileif Jónsdóttir, Henning Bundgaard, Hilma Hólm, Patrick Sulem, Kāri Stefánsson, Karina Banasik, Jakob Thaning Bay, Jens Kjærgaard Boldsen, Thorsten Brodersen, Søren Brunak, Kristoffer Sølvsten Burgdorf, Mona Ameri Chalmer, Maria Didriksen, Khoa Manh Dinh, Joseph Dowsett, Christian Erikstrup, Bjarke Feenstra, Frank Geller, Daníel F. Guðbjartsson, Thomas Folkmann Hansen, Lotte Hindhede, Henrik Hjalgrim, Rikke Louise Jacobsen, Gregor B. E. Jemec, Bitten Aagaard Jensen, Kathrine Agergård Kaspersen, Bertram Kjerulff, Lisette J. A. Kogelman, Margit Anita Hørup Larsen, Ioannis Louloudis, Agnete Troen Lundgaard, Christina Mikkelsen, Christina Mikkelsen, Janna Nissen, Mette Nyegaard, Sisse Rye Ostrowski, Ole Birger Pedersen, Alexander Pil Henriksen, Palle Duun Rohde, Klaus Rostgaard, Michael Schwinn, Hreinn Stefánsson, Hreinn Stefánsson, Erik Sørensen, Unnur Þorsteinsdóttir, Lise Wegner Thørner, Mie Topholm Bruun, Henrik Ullum, Thomas Werge, David Westergaard

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Concepts: Medicine, Locus (genetics), Gene, Genetics, Interleukin, Pericarditis, Immunology, Internal medicine, Cytokine, Biology

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Cited by: 21

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