title: Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic.
abstract: Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9) OR 0.77), ZNF365 (rs10995245 max P = 1.2 × 10(-11) OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9) OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9) beta -1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10) OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.
authors.affiliation: Department of Pulmonary, Critical Care Medicine, Peking University People's Hospital, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Juliette
authors.initials: J
authors.lastname: Faraco
authors.forename: Xiao Song
authors.initials: XS
authors.lastname: Dong
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Ollila
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Pei
authors.initials: P
authors.lastname: An
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Ke Wei
authors.initials: KW
authors.lastname: Jiang
authors.forename: Zhan Cheng
authors.initials: ZC
authors.lastname: Gao
authors.forename: Long
authors.initials: L
authors.lastname: Zhao
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.forename: Ya Nan
authors.initials: YN
authors.lastname: Liu
authors.forename: Qing Hua
authors.initials: QH
authors.lastname: Li
authors.forename: Xiao Zhe
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Wang
authors.forename: Yun Hui
authors.initials: YH
authors.lastname: Lu
authors.forename: Chang Jun
authors.initials: CJ
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Joachim
authors.initials: J
authors.lastname: Hallmayer
authors.forename: Yu Shu
authors.initials: YS
authors.lastname: Huang
authors.forename: Kingman P
authors.initials: KP
authors.lastname: Strohl
authors.forename: Thomas
authors.initials: T
authors.lastname: Pollmächer
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
mesh_terms: D017668:Age of Onset; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics; D055106:Genome-Wide Association Study; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity; D007251:Influenza, Human / Q000150:complications / Q000235:genetics* / Q000473:pathology; D053710:Interleukin-10 Receptor beta Subunit / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009290:Narcolepsy / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics; D000068797:Orexins; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; C507964:IFNAR1 protein, human; C081846:IL10RB protein, human; D053710:Interleukin-10 Receptor beta Subunit; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; C475725:ZNF365 protein, human; D053633:Receptor, Interferon alpha-beta