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.

Public Health Relevance

This research will examine the prevalence and incidence of narcolepsy within the Kaiser Permanente Northern California population. It will also assess how selected environmental and past health factors may be associated with the risk of developing narcolepsy. The multi-disciplinary team will work with the other projects to help understand what causes narcolepsy and provide direction to ways in which it may be treated.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Stanford University
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