The Genetics of Narcolepsy

Dorothée Chabas, Shahrad Taheri, Corinne Renier, Emmanuel Mignot

Research output: Contribution to journalReview article

93 Citations (Scopus)

Abstract

Human narcolepsy is a genetically complex disorder. Family studies indicate a 20-40 times increased risk of narcolepsy in first-degree relatives and twin studies suggest that nongenetic factors also play a role. The tight association between narcolepsy-cataplexy and the HLA allele DQB1*0602 suggests that narcolepsy has an autoimmune etiology. In recent years, extensive genetic studies in animals, using positional cloning in dogs and gene knockouts in mice, have identified abnormalities in hypothalamic hypocretin (orexin) neurotransmission as key to narcolepsy pathophysiology. Though most patients with narcolepsy-cataplexy are hypocretin deficient, mutations or polymorphisms in hypocretin-related genes are extremely rare. It is anticipated that susceptibility genes that are independent of HLA and impinge on the hypocretin neurotransmitter system are isolated in human narcolepsy.

Original languageEnglish
Pages (from-to)459-483
Number of pages25
JournalAnnual Review of Genomics and Human Genetics
Volume4
DOIs
Publication statusPublished - 20 Nov 2003

    Fingerprint

Keywords

  • Autoimmune
  • Human leukocyte antigen (HLA)
  • Hypocretin
  • Hypothalamus
  • Orexin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this