Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | Nature Genetics |
Vol/bind | 42 |
Udgave nummer | 9 |
Sider (fra-til) | 786-9 |
Antal sider | 4 |
ISSN | 1061-4036 |
DOI | |
Status | Udgivet - 1 sep. 2010 |
ID: 34190289