Hor, Hyun and Kutalik, Zoltan and Dauvilliers, Yves and Valsesia, Armand and Lammers, Gert J. and Donjacour, Claire E. H. M. and Iranzo, Alex and Santamaria, Joan and Adrados, Rosa Peraita and Vicario, Jose L. and Overeem, Sebastiaan and Arnulf, Isabelle and Theodorou, Ioannis and Jennum, Poul and Knudsen, Stine and Bassetti, Claudio and Mathis, Johannes and Lecendreux, Michel and Mayer, Geert and Geisler, Peter and Beneto, Antonio and Petit, Brice and Pfister, Corinne and Buerki, Julie Vienne and Didelot, Gerard and Billiard, Michel and Ercilla, Guadalupe and Verduijn, Willem and Claas, Frans H. J. and Vollenwider, Peter and Waeber, Gerard and Waterworth, Dawn M. and Mooser, Vincent and Heinzer, Raphael and Beckmann, Jacques S. and Bergmann, Sven and Tafti, Mehdi (2010) Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. NATURE GENETICS, 42 (9). 786-U80. ISSN 1061-4036, 1546-1718
Full text not available from this repository. (Request a copy)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*03DQB1*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: | Article |
|---|---|
| Uncontrolled Keywords: | COPY NUMBER VARIATION; SLEEP-DISORDERS; CATAPLEXY; GENETICS; DISEASES; RISK; 2ND; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Universitäres Schlafmedizinisches Zentrum Regensburg - Donaustauf |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2020 07:02 |
| Last Modified: | 15 Jul 2020 07:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24273 |
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