Ollila, Hanna M. and Sharon, Eilon and Lin, Ling and Sinnott-Armstrong, Nasa and Ambati, Aditya and Yogeshwar, Selina M. and Hillary, Ryan P. and Jolanki, Otto and Faraco, Juliette and Einen, Mali and Luo, Guo and Zhang, Jing and Han, Fang and Yan, Han and Dong, Xiao Song and Li, Jing and Zhang, Jun and Hong, Seung-Chul and Kim, Tae Won and Dauvilliers, Yves and Barateau, Lucie and Lammers, Gert Jan and Fronczek, Rolf and Mayer, Geert and Santamaria, Joan and Arnulf, Isabelle and Knudsen-Heier, Stine and Bredahl, May Kristin Lyamouri and Thorsby, Per Medboe and Plazzi, Giuseppe and Pizza, Fabio and Moresco, Monica and Crowe, Catherine and Van den Eeden, Stephen K. and Lecendreux, Michel and Bourgin, Patrice and Kanbayashi, Takashi and Martinez-Orozco, Francisco J. and Peraita-Adrados, Rosa and Beneto, Antonio and Montplaisir, Jacques and Desautels, Alex and Huang, Yu-Shu and FinnGen, Poul Jennum and Jennum, Poul and Nevsimalova, Sona and Kemlink, David and Iranzo, Alex and Overeem, Sebastiaan and Wierzbicka, Aleksandra and Geisler, Peter and Sonka, Karel and Honda, Makoto and Hoegl, Birgit and Stefani, Ambra and Coelho, Fernando Morgadinho and Mantovani, Vilma and Feketeova, Eva and Wadelius, Mia and Eriksson, Niclas and Smedje, Hans and Hallberg, Par and Hesla, Per Egil and Rye, David and Pelin, Zerrin and Ferini-Strambi, Luigi and Bassetti, Claudio L. and Mathis, Johannes and Khatami, Ramin and Aran, Adi and Nampoothiri, Sheela and Olsson, Tomas and Kockum, Ingrid and Partinen, Markku and Perola, Markus and Kornum, Birgitte R. and Rueger, Sina and Winkelmann, Juliane and Miyagawa, Taku and Toyoda, Hiromi and Khor, Seik-Soon and Shimada, Mihoko and Tokunaga, Katsushi and Rivas, Manuel and Pritchard, Jonathan K. and Risch, Neil and Kutalik, Zoltan and O'Hara, Ruth and Hallmayer, Joachim and Ye, Chun Jimmie and Mignot, Emmanuel J. (2023) Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy. NATURE COMMUNICATIONS, 14 (1): 2709. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)Abstract
Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement. 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 (R). 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 (R).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; HLA-DQ; GENOTYPE IMPUTATION; CONFER RISK; EXPRESSION; RECONSTRUCTION; TRANSCRIPTOME; EPIDEMIOLOGY; VACCINATION; PROTECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 06:44 |
| Last Modified: | 30 Jan 2024 06:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60999 |
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