ArticleNature genetics2009
Narcolepsy is strongly associated with the T-cell receptor alpha locus.
Article in Nature genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 194 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
194 citing papers in PubMed, 2 syntheses or guidelines pooled it, 480 citations in OpenAlex.
- Abundant pleiotropy in human complex diseases and traits.American journal of human genetics · 2011Pooled it
- Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study.PLoS genetics · 2011Pooled it
- A variant at 9q34.11 is associated with HLA-DQB1*06:02 negative essential hypersomnia.Journal of human genetics · 2018Trial
- Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial.PloS one · 2013Trial
- Immunocyte phenotypes underlying the causal autoimmune features in narcolepsy type 1.Journal of thoracic disease · 2026Article
- A multi-ethnic reference map of T cell receptor germline diversity reveals evidence of natural selection on alpha chain genes.Nature communications · 2026Article
- Recent Advances and Emerging Pharmacotherapeutic Approaches for Central Hypersomnolence Disorders.Clinical pharmacology : advances and applications · 2026Review
- Article
- A Comprehensive Review of Current and Emerging Treatments for Narcolepsy Type 1.Journal of clinical medicine · 2025Review
- Narcolepsy as a potential risk factor for Schizophrenia.Translational psychiatry · 2025Article
- The Role of T Cells in the Pathogenesis of Narcolepsy Type 1: A Narrative Review.International journal of molecular sciences · 2024Review
- Prevalence and Course of Idiopathic Hypersomnia in the Wisconsin Sleep Cohort Study.Neurology · 2024Article
- Correlation analysis between HLA-DQA1*0102/DQB1*0602 genotypes and narcolepsy patients in China.Frontiers in neurology · 2024Article
- The immunopathogenesis of narcolepsy type 1.Nature reviews. Immunology · 2024Review
- Associations between T-cell traits and narcolepsy type 1: new insights from a Mendelian randomization study.Frontiers in neurology · 2024Article
- A series of 7 cases of patients with narcolepsy with hypocretin deficiency without the HLA DQB1*06:02 allele.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2023Article
- Exploring the Literature on Narcolepsy: Insights into the Sleep Disorder That Strikes during the Day.NeuroSci · 2023Review
- Narcolepsy type I-associated DNA methylation and gene expression changes in the human leukocyte antigen region.Scientific reports · 2023Article
- Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.Nature communications · 2023Article
- Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
134 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issuedHong, Sheng Seung-Chul [corrected to Hong, Seung-Chul]
Authors and funding
49 authors at 20 institutions in 9 countries.
Funding
Abstract
Narcolepsy with cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals. Narcolepsy was first shown to be tightly associated with HLA-DR2 (ref. 3) and later sublocalized to DQB1*0602 (ref. 4). Following studies in dogs and mice, a 95% loss of hypocretin-producing cells in postmortem hypothalami from narcoleptic individuals was reported. Using genome-wide association (GWA) in Caucasians with replication in three ethnic groups, we found association between narcolepsy and polymorphisms in the TRA@ (T-cell receptor alpha) locus, with highest significance at rs1154155 (average allelic odds ratio 1.69, genotypic odds ratios 1.94 and 2.55, P < 10(-21), 1,830 cases, 2,164 controls). This is the first documented genetic involvement of the TRA@ locus, encoding the major receptor for HLA-peptide presentation, in any disease. It is still unclear how specific HLA alleles confer susceptibility to over 100 HLA-associated disorders; thus, narcolepsy will provide new insights on how HLA-TCR interactions contribute to organ-specific autoimmune targeting and may serve as a model for over 100 other HLA-associated disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.