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, 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, Als, Thomas Damm, Ziemann, Adam, Abbasi, Ali, Lehtonen, Anne, Lertratanakul, Apinya, Riley-Gillis, Bridget, Rahimov, Fedik, Jacob, Howard, Waring, Jeffrey, Liu, Mengzhen, Smaoui, Nizar, Popovic, Relja, Platt, Adam, Matakidou, Athena, Challis, Benjamin, Paul, Dirk, Lassi, Glenda, Tachmazidou, Ioanna, Hakanen, Antti, Schleutker, Johanna, Pitkänen, Nina, Terho, Perttu, Virolainen, Petri, Mannermaa, Arto, Kosma, Veli-Matti, Chen, Chia-Yen, Runz, Heiko, John, Sally, Lahdenperä, Sanni, Loomis, Stephanie, Eaton, Susan, Okafo, George, Salminen-Mankonen, Heli, Jung, Marc, Lawless, Nathan, Ding, Zhihao, Maranville, Joseph, Hochfeld, Marla, Plenge, Robert, Biswas, Shameek, Kanai, Masahiro, Maasha, Mutaamba, Zhou, Wei, Tuovila, Outi, Pakkanen, Raimo, Laukkanen, Jari, Kuopio, Teijo, Aittomäki, Kristiina, Mäkitie, Antti, Pujol, Natalia, Laisk, Triin, Aalto-Setälä, Katriina, Mäkelä, Johanna, Hautalahti, Marco, Smith, Sarah, Southerington, Tom, Kangasniemi, Eeva, Palin, Henna, Kähönen, Mika, Siltanen, Sanna, Laitinen, Tarja, Vaura, Felix, Suvisaari, Jaana, Niiranen, Teemu, Salomaa, Veikko, Partanen, Jukka, Arvas, Mikko, Ritari, Jarmo, Hyvärinen, Kati, Choy, David, Teng, Edmond, Strauss, Erich, Chen, Hao, Chen, Hubert, Schutzman, Jennifer, Hunkapiller, Julie, Mccarthy, Mark, Bowers, Natalie, Pendergrass, Rion, Lu, Tim, Chu, Audrey, Kulkarni, Diptee, Xu, Fanli, Betts, Joanna, Eicher, John, Gordillo, Jorge Esparza, Addis, Laura, Mccarthy, Linda, Mishra, Rajashree, Kumar, Janet, Ehm, Margaret, G, Auro, Kirsi, Pulford, David, Pitkäranta, Anne, Loukola, Anu, Punkka, Eero, Linna, Malla-Maria, Carpén, Olli, Raivio, Taneli, Turunen, Joni, A, Mäkelä, Tomi, P, Salminen, Aino, Aarnisalo, Antti, Gordin, Daniel, Rice, David, Isometsä, Erkki, Salminen, Eveliina, Joensuu, Heikki, Kalliala, Ilkka, Mattson, Johanna, Sinisalo, Juha, Koskela, Jukka, Eklund, Kari, Hannula-Jouppi, Katariina, Aaltonen, Lauri, Taskinen, Marja-Riitta, Färkkilä, Martti, Raivio, Minna, Heikinheimo, Oskari, Kauppi, Paula, Nieminen, Pekka, Tienari, Pentti, Pussinen, Pirkko, Pikkarainen, Sampsa, Ollila, Terhi, Tuomi, Tiinamaija, Hiltunen, Timo, Meretoja, Tuomo, Salo, Tuula, Palotie, Ulla, Palomäki, Antti, Aittokallio, Jenni, Rinne, Juha, Metsärinne, Kaj, Elenius, Klaus, Pirilä, Laura, Koulu, Leena, Voutilainen, Markku, Lahesmaa, Riitta, Kallionpää, Roosa, Peltonen, Sirkku, Willberg, Tytti, Gursoy, Ulvi, Jokimaa, Varpu, Palotie, Aarno, Kytölä, Anastasia, Ganna, Andrea, Jalanko, Anu, Liu, Aoxing, Lehisto, Arto, Ghazal, Awaisa, Kilpeläinen, Elina, Widen, Elisabeth, Saarentaus, Elmo, Pitkänen, Esa, Laivuori, Hannele, Heyne, Henrike, Shen, Huei-Yi, Kaprio, Jaakko, Rämö, Joel, Karjalainen, Juha, Mehtonen, Juha, Pitkänen, Jyrki, Pärn, Kalle, Donner, Kati, Kivinen, Katja, Lahtela, L. Elisa, Niemi, Mari, E, Kaunisto, Mari, Kals, Mart, Reeve, Mary Pat, Aavikko, Mervi, Mars, Nina, Dada, Oluwaseun Alexander, Della Briotta Parolo, Pietro, Palta, Priit, Weldatsadik, Rigbe, Kajanne, Risto, Rodosthenous, Rodos, Ripatti, Samuli, Ruotsalainen, Sanni, Strausz, Satu, Hassan, Shabbeer, Padmanabhuni, Shanmukha Sampath, Luo, Shuang, Lemmelä, Susanna, Tukiainen, Taru, Sipilä, Timo, P, Kiiskinen, Tuomo, Llorens, Vincent, Daly, Mark, Lee, Jiwoo, Tsuo, Kristin, Kurki, Mitja, Elliott, Amanda, Havulinna, Aki, Partanen, Juulia, Yang, Robert, Reilly, Dermot, Porello, Alessandro, Hart, Amy, Waterworth, Dawn, Khramtsova, Ekaterina, He, Karen, Guan, Meijian, Li, Qingqin, S, Vuoti, Sauli, Green, Eric, Graham, Robert, Mozaffari, Sahar, Huertas-Vazquez, Adriana, Loboda, Andrey, Fox, Caroline, Farias, Fabiana, Sul, Jae-Hoon, Miller, Jason, Raghavan, Neha, Longerich, Simonne, Kettunen, Johannes, Serpi, Raisa, Hinttala, Reetta, Mantere, Tuomo, Remes, Anne, Rahikkala, Elisa, Huhtakangas, Johanna, Tasanen, Kaisa, Huilaja, Laura, Morin-Papunen, Laure, Niinimäki, Maarit, Vääräsmäki, Marja, Uimari, Outi, Karihtala, Peeter, Piltonen, Terhi, Harju, Terttu, Blomster, Timo, Anttonen, Vuokko, Soininen, Hilkka, Kaarniranta, Kai, Suominen, Liisa, Pelkonen, Margit, Siponen, Maria, Kiviniemi, Mikko, Kaipiainen-Seppänen, Oili, Auvinen, Päivi, Mäntylä, Päivi, Kälviäinen, Reetta, Julkunen, Valtteri, O’donnell, Chris, Renaud, Nicole, Ngo, Debby, Mouded, Majd, Mendelson, Mike, Mälarstig, Anders, Lehtonen, Heli, Parkkinen, Jaakko, Kalpala, Kirsi, Miller, Melissa, Bing, Nan, Mcdonough, Stefan, Hu, Xinli, Wu, Ying, Jussila, Airi, Auranen, Annika, Bizaki-Vallaskangas, Argyro, Uusitalo, Hannu, Peltola, Jukka, Hernesniemi, Jussi, Kaukinen, Katri, Kotaniemi-Talonen, Laura, Isomäki, Pia, Salmi, Teea, Kurra, Venla, Sipilä, Kirsi, Toivola, Auli, Järvensivu, Elina, Kaiharju, Essi, Mattsson, Hannele, Kristiansson, Kati, Männikkö, Lotta, Laukkanen, Markku, Brunfeldt, Minna, Laiho, Päivi, Wong, Regis, Koskelainen, Sami, Lähteenmäki, Sini, Soini, Sirpa, Paajanen, Teemu, Kilpi, Terhi, Hiekkalinna, Tero, Sistonen, Tuuli, Chatelain, Clément, Raipal, Deepak, Klinger, Katherine, Lessard, Samuel, Åberg, Fredrik, Hiltunen, Mikko, Heikkinen, Sami, Kankaanranta, Hannu, Palotie, Tuula, Hovatta, Iiris, Palin, Kimmo, Välimäki, Niko, Toppila-Salmi, Sanna, Laakkonen, Eija, Sliz, Eeva, Silven, Heidi, Pylkäs, Katri, Karjalainen, Minna, Arffman, Riikka, Savukoski, Susanna, Tyrmi, Jaakko, Siirtola, Harri, Vähätalo, Iida, Garcia-Tabuenca, Javier, Niemi, Marianna, Helminen, Mika, Luukkaala, Tiina, Ehm, Margaret G, Turunen, Joni A, Mäkelä, Tomi P, Ollila, Hanna, Lahtela, L Elisa, Niemi, Mari E, Parolo, Pietro Della Briotta, Sipilä, Timo P, Li, Qingqin S, O'Donnell, Chris, Obeidat, Ma En

doi:10.48350/182610

<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>

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

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