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猝厥，由强烈情绪引发的间歇性肌肉张力丧失。这种疾病通常在青春期表现出来。几乎所有嗜睡症患者都携带DQB1*0602基因，这是一种与嗜睡症相关的单倍型HLA标记。与其他研究者一样，我们假设，尽管遗传因素可能使人易患发作性睡病，但从怀孕到青春期的环境暴露对该病的表现至关重要。

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.