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 with four interrelated epidemiologic studies. First of all, we will estimate the prevalence of narcolepsy using several overlapping methods of case ascertainment and create a registry of all patients who have narcolepsy, as of 2001 July 1, among the close to 1.7 million residents of King County, Washington. Secondly, we will characterize the clinical features and functional consequences of narcolepsy in all patients in the narcolepsy registry. Thirdly, we will survey sleep complaints among a sample of King County residents identified through random-digit dialing. We will determine whether or not these subjects carry a marker for narcolepsy susceptibility, namely the DQB1 0602 gene. If any patients with narcolepsy are identified, they will be added to the narcolepsy registry. For subjects without narcolepsy, the study will yield estimates for the prevalence of sleep complaints among those who do and do not carry the DQB1 0602 gene in this sample of the general population. Finally, and most importantly, we will evaluate potential risk factors for narcolepsy by means of a population-based case-control study. Cases will come from patients in the narcolepsy registry, and control subjects will be the subset of those identified through random-digit dialing who carry the DQB1 0602 gene. We will assess environmental risk factors in genetically susceptible individuals by requiring all subjects, both cases and controls, to carry the DQB1 0602 gene. Exposures occurring before late adolescence, especially to chemicals that can affect brain function, will be studied. Although narcolepsy is not known to shorten one's life, it is a lifelong disorder that can cause severe disability. The long- term goals of these four interrelated epidemiologic studies are to learn more about the etiology of narcolepsy and to reduce its occurrence by identifying potentially modifiable, risk factors.
