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Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.
Ollila, Hanna M; Sharon, Eilon; Lin, Ling; Sinnott-Armstrong, Nasa; Ambati, Aditya; Yogeshwar, Selina M; Hillary, Ryan P; Jolanki, Otto; Faraco, Juliette; Einen, Mali; Luo, Guo; Zhang, Jing; Han, Fang; Yan, Han; Dong, Xiao Song; Li, Jing; Zhang, Jun; Hong, Seung-Chul; Kim, Tae Won; Dauvilliers, Yves; Barateau, Lucie; Lammers, Gert Jan; Fronczek, Rolf; Mayer, Geert; Santamaria, Joan; Arnulf, Isabelle; Knudsen-Heier, Stine; Bredahl, May Kristin Lyamouri; Thorsby, Per Medbøe; Plazzi, Giuseppe; Pizza, Fabio; Moresco, Monica; Crowe, Catherine; Van den Eeden, Stephen K; Lecendreux, Michel; Bourgin, Patrice; Kanbayashi, Takashi; Martínez-Orozco, Francisco J; Peraita-Adrados, Rosa; Benetó, Antonio; Montplaisir, Jacques; Desautels, Alex; Huang, Yu-Shu; Jennum, Poul; Nevsimalova, Sona; Kemlink, David; Iranzo, Alex; Overeem, Sebastiaan; Wierzbicka, Aleksandra; Geisler, Peter.
Afiliação
  • Ollila HM; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Sharon E; Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.
  • Lin L; Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Sinnott-Armstrong N; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Ambati A; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Yogeshwar SM; Department of Biology, Stanford University, Stanford, CA, 94305, USA.
  • Hillary RP; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Jolanki O; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Faraco J; Department of Biology, Stanford University, Stanford, CA, 94305, USA.
  • Einen M; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Luo G; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Zhang J; Department of Neurology, Charité-Universitätsmedizin, 10117, Berlin, Germany.
  • Han F; Charité-Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, 10117, Berlin, Germany.
  • Yan H; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Dong XS; Department of Genetics, Stanford University, Stanford, CA, 94305, USA.
  • Li J; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Zhang J; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Hong SC; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Kim TW; Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA.
  • Dauvilliers Y; Division of Sleep Medicine, The Peking University People's Hospital, Beijing, China.
  • Barateau L; Division of Sleep Medicine, The Peking University People's Hospital, Beijing, China.
  • Lammers GJ; Division of Sleep Medicine, The Peking University People's Hospital, Beijing, China.
  • Fronczek R; Division of Sleep Medicine, The Peking University People's Hospital, Beijing, China.
  • Mayer G; Department of Neurology, The Peking University People's Hospital, Beijing, China.
  • Santamaria J; Department of Psychiatry, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
  • Arnulf I; Department of Psychiatry, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Korea.
  • Knudsen-Heier S; Sleep-Wake Disorders Center, National Reference Network for Narcolepsy, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier; Institute for Neurosciences of Montpellier (INM), INSERM, Université Montpellier 1, Montpellier, France.
  • Bredahl MKL; Sleep-Wake Disorders Center, National Reference Network for Narcolepsy, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier; Institute for Neurosciences of Montpellier (INM), INSERM, Université Montpellier 1, Montpellier, France.
  • Thorsby PM; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
  • Plazzi G; Stichting Epilepsie Instellingen Nederland (SEIN), Sleep-Wake Centre, Heemstede, The Netherlands.
  • Pizza F; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
  • Moresco M; Stichting Epilepsie Instellingen Nederland (SEIN), Sleep-Wake Centre, Heemstede, The Netherlands.
  • Crowe C; Hephata Klinik, Schimmelpfengstr. 6, 34613, Schwalmstadt, Germany.
  • Van den Eeden SK; Philipps Universität Marburg, Baldinger Str., 35043, Marburg, Germany.
  • Lecendreux M; Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain.
  • Bourgin P; Sleep Disorder Unit, Pitié-Salpêtrière Hospital, Assistance Publique-Hopitaux de Paris, 75013, Paris, France.
  • Kanbayashi T; Norwegian Centre of Expertise for Neurodevelopment Disorders and Hypersomnias (NevSom), Department of Rare Disorders, Oslo University Hospital and University of Oslo, Oslo, Norway.
  • Martínez-Orozco FJ; Norwegian Centre of Expertise for Neurodevelopment Disorders and Hypersomnias (NevSom), Department of Rare Disorders, Oslo University Hospital and University of Oslo, Oslo, Norway.
  • Peraita-Adrados R; Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
  • Benetó A; Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
  • Montplaisir J; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
  • Desautels A; IRCCS Institute of Neurological Sciences, Bologna, Italy.
  • Huang YS; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
  • Jennum P; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
  • Nevsimalova S; IRCCS Institute of Neurological Sciences, Bologna, Italy.
  • Kemlink D; Mater Private Hospital, Dublin 7, Ireland.
  • Iranzo A; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
  • Overeem S; Pediatric Sleep Center and National Reference Center for Narcolepsy and Idiopathic Hypersomnia Hospital Robert Debre, Paris, France.
  • Wierzbicka A; Department of Sleep Medicine, Strasbourg University Hospital, Strasbourg University, Strasbourg, France.
  • Geisler P; Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.
Nat Commun ; 14(1): 2709, 2023 05 15.
Article em En | MEDLINE | ID: mdl-37188663
ABSTRACT
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*0301 and DPB1*0402) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*0602 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Autoimunes / Vacinas contra Influenza / Influenza Humana / Vírus da Influenza A Subtipo H1N1 / Narcolepsia Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Autoimunes / Vacinas contra Influenza / Influenza Humana / Vírus da Influenza A Subtipo H1N1 / Narcolepsia Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article