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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;
[...]
Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
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- Medientyp: E-Artikel
- Titel: Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
- Beteiligte: 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; [...]
- Erschienen: Springer Science and Business Media LLC, 2023
- Erschienen in: Nature Communications
- Sprache: Englisch
- DOI: 10.1038/s41467-023-36120-z
- ISSN: 2041-1723
- Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
- Entstehung:
- Anmerkungen:
- Beschreibung: <jats:title>Abstract</jats:title><jats:p>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®.</jats:p>
- Zugangsstatus: Freier Zugang