title: Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study.
abstract: The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.
authors.affiliation: Center for Integrative Genomics (CIG), University of Lausanne, Lausanne, Switzerland.
authors.forename: Gianina
authors.initials: G
authors.lastname: Luca
authors.forename: José
authors.initials: J
authors.lastname: Haba-Rubio
authors.forename: Yves
authors.initials: Y
authors.lastname: Dauvilliers
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Lammers
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Overeem
authors.forename: Claire E
authors.initials: CE
authors.lastname: Donjacour
authors.forename: Geert
authors.initials: G
authors.lastname: Mayer
authors.forename: Sirous
authors.initials: S
authors.lastname: Javidi
authors.forename: Alex
authors.initials: A
authors.lastname: Iranzo
authors.forename: Joan
authors.initials: J
authors.lastname: Santamaria
authors.forename: Rosa
authors.initials: R
authors.lastname: Peraita-Adrados
authors.forename: Hyun
authors.initials: H
authors.lastname: Hor
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Plazzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Poli
authors.forename: Fabio
authors.initials: F
authors.lastname: Pizza
authors.forename: Isabelle
authors.initials: I
authors.lastname: Arnulf
authors.forename: Michel
authors.initials: M
authors.lastname: Lecendreux
authors.forename: Claudio
authors.initials: C
authors.lastname: Bassetti
authors.forename: Johannes
authors.initials: J
authors.lastname: Mathis
authors.forename: Raphael
authors.initials: R
authors.lastname: Heinzer
authors.forename: Poul
authors.initials: P
authors.lastname: Jennum
authors.forename: Stine
authors.initials: S
authors.lastname: Knudsen
authors.forename: Peter
authors.initials: P
authors.lastname: Geisler
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Wierzbicka
authors.forename: Eva
authors.initials: E
authors.lastname: Feketeova
authors.forename: Corinne
authors.initials: C
authors.lastname: Pfister
authors.forename: Ramin
authors.initials: R
authors.lastname: Khatami
authors.forename: Christian
authors.initials: C
authors.lastname: Baumann
authors.forename: Mehdi
authors.initials: M
authors.lastname: Tafti
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000375:Aging; D015992:Body Mass Index; D002385:Cataplexy / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D057210:Delayed Diagnosis; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008297:Male; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D000068797:Orexins; D017286:Polysomnography; D025341:Principal Component Analysis; D012189:Retrospective Studies; D012727:Sex Characteristics; D012737:Sex Factors; D012894:Sleep Stages / Q000502:physiology; D013997:Time Factors; D055815:Young Adult
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins
keywords: age at onset; diagnostic delay; gender; genome-wide association