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, 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; 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; Ollila, Hanna; 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; Obeidat, Ma´en; 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; Perola, Markus; 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; Rivas, Manuel; Siirtola, Harri; Vähätalo, Iida; Garcia-Tabuenca, Javier; Niemi, Marianna; Helminen, Mika; Luukkaala, Tiina; 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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- Institutt for klinisk medisin [10814]
- CRIStin høstingsarkiv [31446]
Original version
Nature Communications. 2023, 14 (1):2709, DOI: https://doi.org/10.1038/s41467-023-36120-zAbstract
Abstract 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®.Related items
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(Journal article / Tidsskriftartikkel / PublishedVersion; Peer reviewed, 2018)The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of ...