Summary statistics from a genome-wide association study of narcolepsy

Type 1 narcolepsy (T1N) is a neurological condition, in which the death of hypocretin-producing neurons in the lateral hypothalamus leads to excessive daytime sleepiness and symptoms of abnormal Rapid Eye Movement (REM) sleep. Known triggers for narcolepsy are influenza-A infection and associated immunization during the 2009 H1N1 influenza pandemic. Here, we genotyped all remaining consented narcolepsy cases worldwide and assembled this with the existing genotyped individuals. We used this multi-ethnic sample in genome wide association study (GWAS) to dissect disease mechanisms and interactions with environmental triggers (5,339 cases and 20,518 controls). Overall, we found significant associations with HLA (2 GWA significant subloci) and 11 other loci. Six of these other loci have been previously reported (TRA, TRB, CTSH, IFNAR1, ZNF365 and P2RY11) and five are new (PRF1, CD207, SIRPG, IL27 and ZFAND2A). Strikingly, in vaccination-related cases, GWA significant effects were found in HL..., ,1型发作性睡病（Type 1 narcolepsy, T1N）是一种神经系统疾病，其致病机制为下丘脑外侧区产生食欲素（hypocretin）的神经元死亡，进而引发日间过度嗜睡与异常快速眼动（Rapid Eye Movement, REM）睡眠症状。已知发作性睡病的诱因包括2009年甲型H1N1流感大流行期间的甲型流感病毒A感染及相关免疫接种。本研究对全球范围内所有签署知情同意的剩余发作性睡病病例进行基因分型，并将其与已完成基因分型的个体数据整合。我们采用该多族裔样本开展全基因组关联研究（Genome Wide Association Study, GWAS），以解析疾病发病机制及其与环境诱因的相互作用，本研究共纳入5339例病例与20518例对照。总体而言，我们发现人类白细胞抗原（Human Leukocyte Antigen, HLA）（包含2个全基因组关联显著亚位点）及另外11个基因位点存在显著关联。其中6个位点此前已有报道（TRA、TRB、CTSH、IFNAR1、ZNF365及P2RY11），剩余5个为全新发现位点（PRF1、CD207、SIRPG、IL27及ZFAND2A）。值得注意的是，在与疫苗接种相关的病例中，全基因组关联显著效应在HLA区域被发现……