Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves; Valsesia, Armand; Lammers, Gert J; Donjacour, Claire E H M; Iranzo, Alex; Santamaria, Joan; Peraita Adrados, Rosa; Vicario, José L; Overeem, Sebastiaan; Arnulf, Isabelle; Theodorou, Ioannis; Jennum, Poul; Knudsen, Stine; Bassetti, Claudio; Mathis, Johannes; Lecendreux, Michel; Mayer, Geert; Geisler, Peter; ... (2010). Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nature genetics, 42(9), pp. 786-9. New York, N.Y.: Nature America 10.1038/ng.647
Full text not available from this repository. (Request a copy)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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology |
UniBE Contributor: |
Mathis, Johannes |
ISSN: |
1061-4036 |
Publisher: |
Nature America |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:14 |
Last Modified: |
05 Dec 2022 14:02 |
Publisher DOI: |
10.1038/ng.647 |
PubMed ID: |
20711174 |
Web of Science ID: |
000281388400016 |
URI: |
https://boris.unibe.ch/id/eprint/3372 (FactScience: 207042) |
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