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Hallmayer, J.* ; Faraco, J.* ; Lin, L.* ; Hesselson, S.* ; Winkelmann, J. ; Kawashima, M.* ; Mayer, G.* ; Plazzi, G.* ; Nevsimalova, S.* ; Bourgin, P.* ; Hong, S.S.-C.* ; Honda, Y.* ; Honda, M.* ; Högl, B.* ; Longstreth, W.T. Jr.* ; Montplaisir, J.* ; Kemlink, D.* ; Einen, M.* ; Chen, J.* ; Musone, S.L.* ; Akana, M.* ; Miyagawa, T.* ; Duan, J.* ; Desautels, A.* ; Erhardt, C.* ; Hesla, P.E.* ; Poli, F.* ; Frauscher, B.* ; Jeong, J-H.* ; Lee, S-P.* ; Ton, T.G.N.* ; Kvale, M.* ; Kolesar, L.* ; Dobrovolná, M.* ; Nepom, G.T.* ; Salomon, D.* ; Wichmann, H.-E. ; Rouleau, G.A.* ; Gieger, C. ; Levinson, D.F.* ; Gejman, P.V.* ; Meitinger, T. ; Young, T.* ; Peppard, P.* ; Tokunaga, K.* ; Kwok, P.-Y.* ; Risch, N.* ; Mignot, E.*

Narcolepsy is strongly associated with the T-cell receptor alpha locus.

Nat. Genet. 41, 708-711 (2009)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Narcolepsy with cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals(1,2). Narcolepsy was first shown to be tightly associated with HLA-DR2 (ref. 3) and later sublocalized to DQB1*0602 (ref. 4). Following studies in dogs(5) and mice(6), a 95% loss of hypocretin-producing cells in postmortem hypothalami from narcoleptic individuals was reported(7,8). Using genome-wide association (GWA) in Caucasians with replication in three ethnic groups, we found association between narcolepsy and polymorphisms in the TRA@ (T-cell receptor alpha) locus, with highest significance at rs1154155 (average allelic odds ratio 1.69, genotypic odds ratios 1.94 and 2.55, P < 10(-21), 1,830 cases, 2,164 controls). This is the first documented genetic involvement of the TRA@ locus, encoding the major receptor for HLA-peptide presentation, in any disease. It is still unclear how specific HLA alleles confer susceptibility to over 100 HLA-associated disorders(9); thus, narcolepsy will provide new insights on how HLA-TCR interactions contribute to organ-specific autoimmune targeting and may serve as a model for over 100 other HLA-associated disorders.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter genome-wide association; information; evolution; mutation; region; gene
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Zeitschrift Nature Genetics
Quellenangaben Band: 41, Heft: 6, Seiten: 708-711 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed