Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy-Reference-Cited by-全球学者库

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

Published:2023-05-15 Issue:1 Volume:14 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Ollila Hanna M.,Sharon Eilon^ORCID,Lin Ling,Sinnott-Armstrong Nasa^ORCID,Ambati Aditya^ORCID,Yogeshwar Selina M.,Hillary Ryan P.,Jolanki Otto^ORCID,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^ORCID,Knudsen-Heier Stine,Bredahl May Kristin Lyamouri,Thorsby Per Medbøe^ORCID,Plazzi Giuseppe,Pizza Fabio,Moresco Monica,Crowe Catherine,Van den Eeden Stephen K.^ORCID,Lecendreux Michel,Bourgin Patrice,Kanbayashi Takashi,Martínez-Orozco Francisco J.,Peraita-Adrados Rosa^ORCID,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^ORCID,Kemlink David,Iranzo Alex,Overeem Sebastiaan^ORCID,Wierzbicka Aleksandra,Geisler Peter,Sonka Karel^ORCID,Honda Makoto,Högl Birgit,Stefani Ambra,Coelho Fernando Morgadinho,Mantovani Vilma^ORCID,Feketeova Eva^ORCID,Wadelius Mia^ORCID,Eriksson Niclas^ORCID,Smedje Hans,Hallberg Pär^ORCID,Hesla Per Egil,Rye David,Pelin Zerrin,Ferini-Strambi Luigi,Bassetti Claudio L.,Mathis Johannes,Khatami Ramin,Aran Adi,Nampoothiri Sheela^ORCID,Olsson Tomas,Kockum Ingrid^ORCID,Partinen Markku,Perola Markus,Kornum Birgitte R.^ORCID,Rueger Sina^ORCID,Winkelmann Juliane^ORCID,Miyagawa Taku,Toyoda Hiromi,Khor Seik-Soon^ORCID,Shimada Mihoko,Tokunaga Katsushi,Rivas Manuel^ORCID,Pritchard Jonathan K.,Risch Neil^ORCID,Kutalik Zoltan^ORCID,O’Hara Ruth,Hallmayer Joachim,Ye Chun Jimmie^ORCID,Mignot Emmanuel J.^ORCID,

Abstract

AbstractNarcolepsy 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®.

Funder

Academy of Finland

Sigrid Juséliuksen Säätiö

Finnish Cultural Foundation | Etelä-Karjalan Rahasto

Instrumentariumin Tiedesäätiö

U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke

Charité Universitat medizin Berlin, PhD fellowship

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

National Science Foundation of China | Key Programme

GlaxoSmithKline

Jazz Pharmaceuticals

Publisher