| Literature DB >> 20711174 |
Hyun Hor1, Zoltán Kutalik, Yves Dauvilliers, Armand Valsesia, Gert J Lammers, Claire E H M Donjacour, Alex Iranzo, Joan Santamaria, Rosa Peraita Adrados, José L Vicario, Sebastiaan Overeem, Isabelle Arnulf, Ioannis Theodorou, Poul Jennum, Stine Knudsen, Claudio Bassetti, Johannes Mathis, Michel Lecendreux, Geert Mayer, Peter Geisler, Antonio Benetó, Brice Petit, Corinne Pfister, Julie Vienne Bürki, Gérard Didelot, Michel Billiard, Guadalupe Ercilla, Willem Verduijn, Frans H J Claas, Peter Vollenweider, Peter Vollenwider, Gerard Waeber, Dawn M Waterworth, Vincent Mooser, Raphaël Heinzer, Jacques S Beckmann, Sven Bergmann, Mehdi Tafti.
Abstract
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*03-DQB1*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.Entities:
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Year: 2010 PMID： 20711174 DOI： 10.1038/ng.647
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330