Epidemiology of Human Narcolepsy

发作性睡病是一种睡眠障碍，其特征是白天过度嗜睡和紧张症，由强烈情绪引发的肌肉张力的发作性丧失。这种疾病通常在青春期出现。几乎所有发作性睡病患者都携带DQB 1 *0602基因，这是与发作性睡病相关的单倍型的HLA标记。像其他研究者一样，我们假设，虽然遗传因素可能使人们易患嗜睡症，但受孕和青春期之间的环境暴露对疾病的表达至关重要。 我们建议在北方加州的Kaiser Permanente（KPNC）的一系列研究中检验这一假设并检查发作性睡病的其他流行病学特征。我们的目的是1）根据特征和HLA基因型对所有假定的发作性睡病病例进行分类，2）估计发病率和患病率，3）通过要求所有受试者（病例和对照）携带DQB 1 *0602基因，对遗传易感个体的环境危险因素进行病例对照研究。我们将研究一系列可能改变风险的因素，但重点是青春期后期之前发生的暴露。我们还将为未来的研究建立一个生物储存库。我们将通过对KPNC电子病历的监测和审查，确定2006年至2015年KPNC中所有推定嗜睡症的个体。这些人将接受采访，以获得发作性睡病和相关症状的历史和因素，可能会增加或减少风险。我们还将获得血液生物样本。在最近发病的个体（≥ 2.5岁）中，我们还将获得额外的生物标本。每个人都将接受HLA DQB 1 *0602测试。所有对该标志物检测呈阳性的病例个体将与五个随机选择的对照组相匹配，这些对照组在年龄、性别和KPNC成员资格上相匹配。对照组将接受相同的访谈（无嗜睡症部分），并获得生物标本。此外，我们将从KPNC的一个大型（100，000人）队列中为每个病例选择一个对照，该队列将进行基因分型，并按年龄、性别和HLA DBQ1*0602基因型进行匹配。他们将接受相同的对照面谈。将使用逻辑回归估计与假定风险因素相关的风险。 这些研究的长期目标是更多地了解发作性睡病的病因，并通过识别潜在的可改变的危险因素来减少其发生。

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy, an episodic loss of muscle tone triggered by intense emotions. The disease usually manifests by adolescence. Almost all patients with narcolepsy carry the DQB1*0602 gene, an HLA marker for the haplotype associated with narcolepsy. Like other investigators, we hypothesize that although genetic factors may predispose people to develop narcolepsy, environmental exposures between conception and adolescence are essential for expression of the disease. We propose to test this hypothesis and examine other epidemiologic features of narcolepsy in a series of studies in Kaiser Permanente Northern California (KPNC). Our aims are to 1) classify all putative narcolepsy cases by characteristics and HLA genotype, 2) estimate the incidence and prevalence, and 3) conduct a case-control study of environmental risk factors in genetically susceptible individuals by requiring all subjects, both cases and controls, to carry the DQB1*0602 gene. We will examine a range of factors that may alter risk, but with a focus on exposures occurring before late adolescence. We will also establish a biorepository for future research. We will identify all individuals with presumptive narcolepsy in KPNC from 2006 to 2015 by means of surveillance and review of KPNC electronic medical records. These individuals will be interviewed to obtain history on narcolepsy and related symptoms and factors that may increase or decrease risk. We will also obtain a blood biospecimen. Among individuals with recent onset (^2.5 years) we will also obtain additional biospecimens. Each individual will undergo HLA DQB1*0602 testing. All case individuals who test positive for this marker will be matched to five randomly selected controls matched on age, sex and membership in KPNC. The controls will undergo the same interview without the narcolepsy portion and have a biospecimen obtained. In addition, we will select one control per case from a large (100,000 person) cohort at KPNC that will have been genotyped, and match by age, sex and HLA DBQ1*0602 genotype. They will undergo the same control interview. Logistic regression will be used to estimate the risk associated with putative risk factors. The long-term goals of these studies are to learn more about the etiology of narcolepsy and to reduce its occurrence by identifying potentially modifiable risk factors.