학술논문
Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
Document Type
article
Author
Hanna M. Ollila; Eilon Sharon; Ling Lin; Nasa Sinnott-Armstrong; Aditya Ambati; Selina M. Yogeshwar; Ryan P. Hillary; Otto Jolanki; Juliette Faraco; Mali Einen; Guo Luo; Jing Zhang; Fang Han; Han Yan; Xiao Song Dong; Jing Li; Jun Zhang; Seung-Chul Hong; Tae Won Kim; Yves Dauvilliers; Lucie Barateau; Gert Jan Lammers; Rolf Fronczek; Geert Mayer; Joan Santamaria; Isabelle Arnulf; Stine Knudsen-Heier; May Kristin Lyamouri Bredahl; Per Medbøe Thorsby; Giuseppe Plazzi; Fabio Pizza; Monica Moresco; Catherine Crowe; Stephen K. Van den Eeden; Michel Lecendreux; Patrice Bourgin; Takashi Kanbayashi; Francisco J. Martínez-Orozco; Rosa Peraita-Adrados; Antonio Benetó; Jacques Montplaisir; Alex Desautels; Yu-Shu Huang; FinnGen; Poul Jennum; Sona Nevsimalova; David Kemlink; Alex Iranzo; Sebastiaan Overeem; Aleksandra Wierzbicka; Peter Geisler; Karel Sonka; Makoto Honda; Birgit Högl; Ambra Stefani; Fernando Morgadinho Coelho; Vilma Mantovani; Eva Feketeova; Mia Wadelius; Niclas Eriksson; Hans Smedje; Pär Hallberg; Per Egil Hesla; David Rye; Zerrin Pelin; Luigi Ferini-Strambi; Claudio L. Bassetti; Johannes Mathis; Ramin Khatami; Adi Aran; Sheela Nampoothiri; Tomas Olsson; Ingrid Kockum; Markku Partinen; Markus Perola; Birgitte R. Kornum; Sina Rueger; Juliane Winkelmann; Taku Miyagawa; Hiromi Toyoda; Seik-Soon Khor; Mihoko Shimada; Katsushi Tokunaga; Manuel Rivas; Jonathan K. Pritchard; Neil Risch; Zoltan Kutalik; Ruth O’Hara; Joachim Hallmayer; Chun Jimmie Ye; Emmanuel J. Mignot
Source
Nature Communications, Vol 14, Iss 1, Pp 1-13 (2023)
Subject
Language
English
ISSN
2041-1723
Abstract
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®.