Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

Hyun Hor; Zoltan Kutalik; Yves Dauvilliers; Armand Valsesia; Gert J. Lammers; Claire E. H. M. Donjacour; Alex Iranzo; Joan Santamaria; Rosa Peraita Adrados; Jose L. Vicario; Sebastiaan Overeem; Isabelle Arnulf; Ioannis Theodorou; Poul Jennum; Stine Knudsen; Claudio Bassetti; Johannes Mathis; Michel Lecendreux; Geert Mayer; Peter Geisler; Antonio Beneto; Brice Petit; Corinne Pfister; Julie Vienne Buerki; Gerard Didelot; Michel Billiard; Guadalupe Ercilla; Willem Verduijn; Frans H. J. Claas; Peter Vollenwider; Gerard Waeber; Dawn M. Waterworth; Vincent Mooser; Raphael Heinzer; Jacques S. Beckmann; Sven Bergmann; Mehdi Tafti

doi:10.1038/ng.647

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Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

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Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

Hyun Hor, Zoltan Kutalik, Yves Dauvilliers, Armand Valsesia, Gert J. Lammers, Claire E. H. M. Donjacour, Alex Iranzo, Joan Santamaria, Rosa Peraita Adrados, Jose L. Vicario, …

Nature genetics, Vol.42(9), pp.786-U80

01/09/2010

DOI: https://doi.org/10.1038/ng.647

PMID: 20711174

Résumé

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB1*1501-DQB1*0602. We found association with a protective variant near HLA-DQA2 (rs2858884; P < 3 x 10(-8)). Further analysis revealed that rs2858884 is strongly linked to DRB1*03DQB1*02 (P < 4 x 10(-43)) and DRB1*1301-DQB1*0603 (P < 3 x 10(-7)). Cases almost never carried a trans DRB1*1301-DQB1*0603 haplotype (odds ratio = 0.02; P < 6 x 10(-14)). This unexpected protective HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility.

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Titre: Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy
Créateurs - sans rôle: Hyun Hor - Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland
Zoltan Kutalik - Univ Lausanne, Dept Med Genet, Lausanne, Switzerland
Yves Dauvilliers - Inserm
Armand Valsesia - Univ Lausanne, Dept Med Genet, Lausanne, Switzerland
Gert J. Lammers - Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands
Claire E. H. M. Donjacour - Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands
Alex Iranzo - Hosp Clin Barcelona, Neurol Serv, Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Joan Santamaria - Hosp Clin Barcelona, Neurol Serv, Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Rosa Peraita Adrados - Gregorio Maranon Univ Hosp, Sleep & Epilepsy Unit, Dept Clin Neurophysiol, Madrid, Spain
Jose L. Vicario - Blood Ctr Community Madrid, Madrid, Spain
Sebastiaan Overeem - Sleep Med Ctr Kempenhaeghe, Heeze, Netherlands
Isabelle Arnulf - Hop La Pitie Salpetriere, Sleep Disorders Unit, Natl Reference Network Orphan Dis Narcolepsy & Id, Paris, France
Ioannis Theodorou - Inserm
Poul Jennum - University of Copenhagen
Stine Knudsen - Univ Copenhagen, Dept Clin Neurophysiol, Glostrup, Denmark
Claudio Bassetti - Osped Civico, Neuroctr Ente Osped Cantonale Svizzera Italiana, Lugano, Switzerland
Johannes Mathis - University of Bern
Michel Lecendreux - Univ Paris 07, Pediat Sleep Ctr, Natl Reference Network Orphan Dis Narcolepsy & Id, Dept Child & Adolescent Psychopathol,Robert Debre, Paris, France
Geert Mayer - Hephata Clin Neurol, Schwalmstadt, Germany
Peter Geisler - Univ Hosp Regensburg, Sleep Disorders & Res Ctr, Dept Psychiat & Psychotherapy, Regensburg, Germany
Antonio Beneto - Hosp Univ La Fe, Unidad Sueno, Serv Neurofisiol Clin, Valencia, Spain
Brice Petit - Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland
Corinne Pfister - University of Lausanne
Julie Vienne Buerki - Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland
Gerard Didelot - Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland
Michel Billiard - Gui de Chauliac Hosp, Dept Neurol, Natl Reference Network Orphan Dis Narcolepsy & Id, Montpellier, France
Guadalupe Ercilla - Hosp Clin Barcelona, Serv Immunol, Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain
Willem Verduijn - Leiden Univ, Med Ctr, Dept Immunohaematol & Blood Transfus, Leiden, Netherlands
Frans H. J. Claas - Leiden Univ, Med Ctr, Dept Immunohaematol & Blood Transfus, Leiden, Netherlands
Peter Vollenwider - CHU Vaudois, Dept Med, Lausanne, Switzerland
Gerard Waeber - CHU Vaudois, Dept Med, Lausanne, Switzerland
Dawn M. Waterworth - GlaxoSmithKline Inc, Div Genet Res & Dev, King Of Prussia, PA USA
Vincent Mooser - GlaxoSmithKline Inc, Div Genet Res & Dev, King Of Prussia, PA USA
Raphael Heinzer - CHU Vaudois, Ctr Invest & Res Sleep, Lausanne, Switzerland
Jacques S. Beckmann - University of Lausanne
Sven Bergmann - University of Lausanne
Mehdi Tafti - University of Lausanne
Détails de publication: Nature genetics, Vol.42(9), pp.786-U80
Éditeur: Springer Nature
Nombre de pages: 5
Note de subvention: Leenaards Foundation European Narcolepsy Network European Framework Project 6 UCB Pharma S.A. (Belgium); UCB Pharma SA GlaxoSmithKline PHRC 2007-P070138 / Agence Nationale de la Recherche-07-MRAR (France); Agence Nationale de la Recherche (ANR) 3100AO-108478/2; 3100AO-116323/1; 310000-112552/1 / Swiss National Science Foundation; Swiss National Science Foundation (SNSF) Giorgi-Cavaglieri Foundation University and the State of Vaud (Switzerland) French Ministry of Research and Higher Education
Identifiants: 99140092209311
Unité académique: Institut des Neurosciences de Montpellier - INM
Langue: English
Type de ressource: Journal article