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

Détails

ID Serval
serval:BIB_CFB40FFC4F99
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy.
Périodique
Nature Genetics
Auteur(s)
Hor H., Kutalik Z., Dauvilliers Y., Valsesia A., Lammers G.J., Donjacour C.E., Iranzo A., Santamaria J., Peraita Adrados R., Vicario J.L., Overeem S., Arnulf I., Theodorou I., Jennum P., Knudsen S., Bassetti C., Mathis J., Lecendreux M., Mayer G., Geisler P., Benetó A., Petit B., Pfister C., Bürki J.V., Didelot G., Billiard M., Ercilla G., Verduijn W., Claas F.H., Vollenweider P., Waeber G., Waterworth D.M., Mooser V., Heinzer R., Beckmann J.S., Bergmann S., Tafti M.
ISSN
1546-1718[electronic], 1061-4036[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
42
Numéro
9
Pages
786-789
Langue
anglais
Résumé
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.
Mots-clé
Adult, Aged, Case-Control Studies, European Continental Ancestry Group/genetics, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-D Antigens/genetics, Haplotypes, Humans, Male, Middle Aged, Narcolepsy/genetics , Colaus Study
Pubmed
Web of science
Création de la notice
22/09/2010 15:59
Dernière modification de la notice
20/08/2019 16:50
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