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DOI 10.1038/s41467-023-36120-z

Медицинская библиотека · Nature communications · 2023

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, FinnGen, Jennum Poul, Nevsimalova Sona, Kemlink David, Iranzo Alex, Overeem Sebastiaan, Wierzbicka Aleksandra, Geisler Peter, Sonka Karel, Honda Makoto, Högl Birgit, Stefani Ambra, Coelho Fernando Morgadinho, Mantovani Vilma, Feketeova Eva, Wadelius Mia, Eriksson Niclas, Smedje Hans, Hallberg Pär, Hesla Per Egil, Rye David, Pelin Zerrin, Ferini-Strambi Luigi, Bassetti Claudio L, Mathis Johannes, Khatami Ramin, Aran Adi, Nampoothiri Sheela, Olsson Tomas, Kockum Ingrid, Partinen Markku, Perola Markus, Kornum Birgitte R, Rueger Sina, Winkelmann Juliane, Miyagawa Taku, Toyoda Hiromi, Khor Seik-Soon, Shimada Mihoko, Tokunaga Katsushi, Rivas Manuel, Pritchard Jonathan K, Risch Neil, Kutalik Zoltan, O'Hara Ruth, Hallmayer Joachim, Ye Chun Jimmie, Mignot Emmanuel J

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Аннотация

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®.

Для цитирования: 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, FinnGen, Jennum Poul, Nevsimalova Sona, Kemlink David, Iranzo Alex, Overeem Sebastiaan, Wierzbicka Aleksandra, Geisler Peter, Sonka Karel, Honda Makoto, Högl Birgit, Stefani Ambra, Coelho Fernando Morgadinho, Mantovani Vilma, Feketeova Eva, Wadelius Mia, Eriksson Niclas, Smedje Hans, Hallberg Pär, Hesla Per Egil, Rye David, Pelin Zerrin, Ferini-Strambi Luigi, Bassetti Claudio L, Mathis Johannes, Khatami Ramin, Aran Adi, Nampoothiri Sheela, Olsson Tomas, Kockum Ingrid, Partinen Markku, Perola Markus, Kornum Birgitte R, Rueger Sina, Winkelmann Juliane, Miyagawa Taku, Toyoda Hiromi, Khor Seik-Soon, Shimada Mihoko, Tokunaga Katsushi, Rivas Manuel, Pritchard Jonathan K, Risch Neil, Kutalik Zoltan, O'Hara Ruth, Hallmayer Joachim, Ye Chun Jimmie, Mignot Emmanuel J. Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.. Nature communications. 2023. DOI: 10.1038/s41467-023-36120-z.

Предметные рубрики MeSH

HumansAutoimmunityInfluenza, HumanInfluenza A Virus, H1N1 SubtypeAutoimmune DiseasesInfluenza VaccinesNarcolepsy
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