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Pracoviště: Department of Neurology Charité Universitätsmed...

1 záznamů v PubMed Filtry

Článek

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy

Ollila, Hanna M
Autor Ollila, Hanna M Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
Sharon, Eilon
Autor Sharon, Eilon ORCID Department of Genetics, Stanford University, Stanford, CA, 94305, USA Department of Biology, Stanford University, Stanford, CA, 94305, USA
Lin, Ling
Autor Lin, Ling Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA
Sinnott-Armstrong, Nasa
Autor Sinnott-Armstrong, Nasa ORCID Department of Genetics, Stanford University, Stanford, CA, 94305, USA Department of Biology, Stanford University, Stanford, CA, 94305, USA
Ambati, Aditya
Autor Ambati, Aditya ORCID Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA
Yogeshwar, Selina M
Autor Yogeshwar, Selina M Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA Department of Neurology, Charité-Universitätsmedizin, 10117, Berlin, Germany Charité-Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, 10117, Berlin, Germany
Hillary, Ryan P
Autor Hillary, Ryan P Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA
Jolanki, Otto
Autor Jolanki, Otto ORCID Department of Genetics, Stanford University, Stanford, CA, 94305, USA
Faraco, Juliette
Autor Faraco, Juliette Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA
Einen, Mali
Autor Einen, Mali Stanford University, Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, 94304, USA

Nature communications. 2023 May 15 ; 14 (1) : 2709. [epub] 20230515

Nat Commun
ISSN 2041-1723
Zdroj

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*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 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®.

MeSH
autoimunita genetika MeSH
autoimunitní nemoci * epidemiologie genetika MeSH
chřipka lidská * epidemiologie genetika MeSH
lidé MeSH
narkolepsie * chemicky indukované genetika MeSH
vakcíny proti chřipce * škodlivé účinky MeSH
virus chřipky A, podtyp H1N1 * genetika MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Extramural MeSH
Názvy látek
vakcíny proti chřipce * MeSH

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