DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe

Mehdi Tafti; Hyun Hor; Yves Dauvilliers; Gert J Lammers; Sebastiaan Overeem; Geert Mayer; Sirous Javidi; Alex Iranzo; Joan Santamaria; Rosa Peraita-Adrados; José L Vicario; Isabelle Arnulf; Giuseppe Plazzi; Sophie Bayard; Francesca Poli; Fabio Pizza; Peter Geisler; Aleksandra Wierzbicka; Claudio L Bassetti; Johannes Mathis; Michel Lecendreux; Claire E H M Donjacour; Astrid van der Heide; Raphaël Heinzer; José Haba-Rubio; Eva Feketeova; Birgit Högl; Birgit Frauscher; Antonio Benetó; Ramin Khatami; Francesca Cañellas; Corinne Pfister; Sabine Scholz; Michel Billiard; Christian R Baumann; Guadalupe Ercilla; Willem Verduijn; Frans H J Claas; Valérie Dubois; Jacek Nowak; Hans-Peter Eberhard; Sylvain Pradervand; Charlotte N Hor; Manuela Testi; Jean-Marie Tiercy; Zoltán Kutalik; Behalf of the European Narcolepsy Network (EU-NN)

doi:10.5665/sleep.3300

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DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe

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DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe

Mehdi Tafti, Hyun Hor, Yves Dauvilliers, Gert J Lammers, Sebastiaan Overeem, Geert Mayer, Sirous Javidi, Alex Iranzo, Joan Santamaria, Rosa Peraita-Adrados, …

Sleep (New York, N.Y.), Vol.37(1), pp.19-25

01/01/2014

DOI: https://doi.org/10.5665/sleep.3300

PMID: 24381371

Résumé

Alleles

Cataplexy - genetics

Deoxyribonuclease I - metabolism

Europe - epidemiology

Europe - ethnology

European Continental Ancestry Group - genetics

Exome - genetics

Genetic Predisposition to Disease - genetics

Genome-Wide Association Study

HLA-DQ beta-Chains - genetics

Humans

Influenza A Virus, H1N1 Subtype - immunology

Influenza Vaccines - administration & dosage

Narcolepsy - genetics

Odds Ratio

Polymorphism, Single Nucleotide - genetics

Retrospective Studies

Vaccination

Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. Retrospective case-control study. A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.

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Titre: DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe
Créateurs - sans rôle: Mehdi Tafti
Hyun Hor
Yves Dauvilliers
Gert J Lammers
Sebastiaan Overeem - Kempenhaeghe
Geert Mayer - Hephata-Clinic for Neurology, Schwalmstadt-Treysa, Germany
Sirous Javidi - Hephata-Clinic for Neurology, Schwalmstadt-Treysa, Germany
Alex Iranzo - Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain
Joan Santamaria - Hospital Clínic de Barcelona
Rosa Peraita-Adrados - Sleep and Epilepsy Unit - Clinical Neurophysiology Department, Gregorio Marañón University Hospital, Madrid, Spain
José L Vicario - Histocompatibility, Blood Center of the Community of Madrid, Madrid, Spain
Isabelle Arnulf - Pitié-Salpêtrière Hospital
Giuseppe Plazzi - University of Bologna
Sophie Bayard
Francesca Poli - University of Bologna
Fabio Pizza - University of Bologna
Peter Geisler - University Hospital Regensburg
Aleksandra Wierzbicka - Institute of Psychiatry and Neurology
Claudio L Bassetti - University of Bern
Johannes Mathis - University of Bern
Michel Lecendreux - Pediatric Sleep Center, National Reference Network for Orphan Diseases (Narcolepsy and Idiopathic Hypersomnia), Robert Debré Hospital, Paris VII University, Paris, France
Claire E H M Donjacour - Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
Astrid van der Heide - Leiden University Medical Center
Raphaël Heinzer - Center for Investigation and Research in Sleep (CIRS), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
José Haba-Rubio - Center for Investigation and Research in Sleep (CIRS), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
Eva Feketeova - Department of Neurology, Faculty of Medicine, Safarikiensis University and Louis Pasteur Faculty Hospital Kosice, Kosice, Slovakia
Birgit Högl - Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
Birgit Frauscher - Innsbruck Medical University
Antonio Benetó - Unidad de Sueño, Servicio Neurofisiología Clínica, Hospital Universitario La Fe, Valencia, Spain
Ramin Khatami - Sleep Medicine, Barmelweid Clinic, Switzerland
Francesca Cañellas - Hospital Universitario Son Espases
Corinne Pfister - University of Lausanne
Sabine Scholz - National Reference Network for Orphan Diseases (Narcolepsy and Idiopathic Hypersomnia), Department of Neurology, Guide-Chauliac Hospital, Montpellier, France
Michel Billiard - National Reference Network for Orphan Diseases (Narcolepsy and Idiopathic Hypersomnia), Department of Neurology, Guide-Chauliac Hospital, Montpellier, France
Christian R Baumann - University Hospital of Zurich
Guadalupe Ercilla - Immunology Service, CDB, Hospital Clinic, Barcelona, Spain
Willem Verduijn - Department of Immunohaematology and Blood Trans-fusion, Leiden University Medical Centre, The Netherlands
Frans H J Claas - Department of Immunohaematology and Blood Trans-fusion, Leiden University Medical Centre, The Netherlands
Valérie Dubois - Établissement Français du Sang
Jacek Nowak - Department of Immunogenetics, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
Hans-Peter Eberhard - German National Bone Marrow Donor Registry, Ulm, Germany
Sylvain Pradervand
Charlotte N Hor - Center for Genomic Regulation (CRG), Barcelona, and Universitat Pompeu Fabra (UPF), Barcelona, Spain
Manuela Testi - Laboratory of Immunogenetics and Transplant Biology, IME Foundation-Mediterranean Institute of Hematology, Roma, Italy
Jean-Marie Tiercy - University Hospital of Geneva
Zoltán Kutalik
Behalf of the European Narcolepsy Network (EU-NN)
Détails de publication: Sleep (New York, N.Y.), Vol.37(1), pp.19-25
Identifiants: 99139863109311
Unité académique: Institut des Neurosciences de Montpellier - INM
Langue: English
Type de ressource: Journal article