title: ImmunoChip study implicates antigen presentation to T cells in narcolepsy.
abstract: Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.
authors: Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, California, USA.
authors: Juliette
authors: J
authors: Faraco
authors: Ling
authors: L
authors: Lin
authors: Birgitte Rahbek
authors: BR
authors: Kornum
authors: Eimear E
authors: EE
authors: Kenny
authors: Gosia
authors: G
authors: Trynka
authors: Mali
authors: M
authors: Einen
authors: Tom J
authors: TJ
authors: Rico
authors: Peter
authors: P
authors: Lichtner
authors: Yves
authors: Y
authors: Dauvilliers
authors: Isabelle
authors: I
authors: Arnulf
authors: Michel
authors: M
authors: Lecendreux
authors: Sirous
authors: S
authors: Javidi
authors: Peter
authors: P
authors: Geisler
authors: Geert
authors: G
authors: Mayer
authors: Fabio
authors: F
authors: Pizza
authors: Francesca
authors: F
authors: Poli
authors: Giuseppe
authors: G
authors: Plazzi
authors: Sebastiaan
authors: S
authors: Overeem
authors: Gert Jan
authors: GJ
authors: Lammers
authors: David
authors: D
authors: Kemlink
authors: Karel
authors: K
authors: Sonka
authors: Sona
authors: S
authors: Nevsimalova
authors: Guy
authors: G
authors: Rouleau
authors: Alex
authors: A
authors: Desautels
authors: Jacques
authors: J
authors: Montplaisir
authors: Birgit
authors: B
authors: Frauscher
authors: Laura
authors: L
authors: Ehrmann
authors: Birgit
authors: B
authors: Högl
authors: Poul
authors: P
authors: Jennum
authors: Patrice
authors: P
authors: Bourgin
authors: Rosa
authors: R
authors: Peraita-Adrados
authors: Alex
authors: A
authors: Iranzo
authors: Claudio
authors: C
authors: Bassetti
authors: Wei-Min
authors: WM
authors: Chen
authors: Patrick
authors: P
authors: Concannon
authors: Susan D
authors: SD
authors: Thompson
authors: Vincent
authors: V
authors: Damotte
authors: Bertrand
authors: B
authors: Fontaine
authors: Maxime
authors: M
authors: Breban
authors: Christian
authors: C
authors: Gieger
authors: Norman
authors: N
authors: Klopp
authors: Panos
authors: P
authors: Deloukas
authors: Cisca
authors: C
authors: Wijmenga
authors: Joachim
authors: J
authors: Hallmayer
authors: Suna
authors: S
authors: Onengut-Gumuscu
authors: Stephen S
authors: SS
authors: Rich
authors: Juliane
authors: J
authors: Winkelmann
authors: Emmanuel
authors: E
authors: Mignot
mesh_terms: D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D056726:Genetic Association Studies; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009290:Narcolepsy / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D009479:Neuropeptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000068797:Orexins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D044465:White People
chemical_list: D006680:HLA Antigens; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016693:Receptors, Antigen, T-Cell, alpha-beta