title: Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy.
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.
authors: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors: Hyun
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authors: Hor
authors: Zoltán
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authors: Kutalik
authors: Yves
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authors: Dauvilliers
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authors: Valsesia
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authors: Lammers
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authors: Peraita Adrados
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authors: Mathis
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authors: Geisler
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authors: Benetó
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authors: Petit
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authors: Pfister
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authors: Bürki
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authors: Didelot
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authors: Billiard
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authors: Ercilla
authors: Willem
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authors: Verduijn
authors: Frans H J
authors: FH
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authors: Peter
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authors: Vollenweider
authors: Peter
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authors: Vollenwider
authors: Gerard
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authors: Waeber
authors: Dawn M
authors: DM
authors: Waterworth
authors: Vincent
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authors: Mooser
authors: Raphaël
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authors: Tafti
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006681:HLA-D Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D006681:HLA-D Antigens