Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy.
Details
Serval ID
serval:BIB_CFB40FFC4F99
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy.
Journal
Nature Genetics
ISSN
1546-1718[electronic], 1061-4036[linking]
Publication state
Published
Issued date
2010
Volume
42
Number
9
Pages
786-789
Language
english
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.
Keywords
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
Create date
22/09/2010 15:59
Last modification date
20/08/2019 16:50