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; ... (2023). Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy. Nature communications, 14(1), p. 2709. Nature Publishing Group 10.1038/s41467-023-36120-z
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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®.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology |
UniBE Contributor: |
Bassetti, Claudio L.A., Mathis, Johannes, Khatami, Ramin |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
16 May 2023 15:32 |
Last Modified: |
21 May 2023 02:26 |
Publisher DOI: |
10.1038/s41467-023-36120-z |
PubMed ID: |
37188663 |
BORIS DOI: |
10.48350/182610 |
URI: |
https://boris.unibe.ch/id/eprint/182610 |
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