Tafti, Mehdi and Hor, Hyun and Dauvilliers, Yves and Lammers, Gert J. and Overeem, Sebastiaan and Mayer, Geert and Javidi, Sirous and Iranzo, Alex and Santamaria, Joan and Peraita-Adrados, Rosa and Vicario, Jose L. and Arnulf, Isabelle and Plazzi, Giuseppe and Bayard, Sophie and Poli, Francesca and Pizza, Fabio and Geisler, Peter and Wierzbicka, Aleksandra and Bassetti, Claudio L. and Mathis, Johannes and Lecendreux, Michel and Donjacour, Claire E. H. M. and van der Heide, Astrid and Heinzer, Raphael and Haba-Rubio, Jose and Feketeova, Eva and Hogl, Birgit and Frauscher, Birgit and Beneto, Antonio and Khatami, Ramin and Canellas, Francesca and Pfister, Corinne and Scholz, Sabine and Billiard, Michel and Baumann, Christian R. and Ercilla, Guadalupe and Verduijn, Willem and Claas, Frans H. J. and Dubois, Valerie and Nowak, Jacek and Eberhard, Hans-Peter and Pradervand, Sylvain and Hor, Charlotte N. and Testi, Manuela and Tiercy, Jean-Marie and Kutalik, Zoltan (2014) DQB1 Locus Alone Explains Most of the Risk and Protection in Narcolepsy with Cataplexy in Europe. SLEEP, 37 (1). 19-U228. ISSN 0161-8105, 1550-9109
Full text not available from this repository. (Request a copy)Abstract
Study Objective: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. Design: Retrospective case-control study. Setting: A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10-4 mapping to DHSs. Ten SNPs tagging these sites, HLA-DQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. Patients and Participants: For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. Measurements and Results: None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10-9) and rs1154155 within the TRA locus (P < 2x10-8) replicated. DQB1 typing confirmed that DQB1* 06: 02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1* 06: 03, odds ratio 0.17, DQB1* 05: 01, odds ratio 0.56, DQB1* 06: 09 odds ratio 0.21, DQB1* 02 odds ratio 0.76) were also identified. Conclusion: An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1* 06: 02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; HLA CLASS-II; DQB1-ASTERISK-0602; AUTOANTIBODIES; SUSCEPTIBILITY; VACCINATION; DISEASE; ONSET; DR2; Autoimmunity; GWAS; H1N1 vaccination; genetics |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Nov 2019 09:29 |
| Last Modified: | 29 Nov 2019 09:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/11029 |
Actions (login required)
 |
View Item |
