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Kornum, B.R.* ; Kawashima, M.* ; Faraco, J.* ; Lin, L.* ; Rico, T.J.* ; Hesselson, S.* ; Axtell, RC.* ; Kuipers, H.* ; Weiner, K.* ; Hamacher, A.* ; Kassack, M.U.* ; Han, F.* ; Knudsen, S.* ; Li, J.* ; Dong, X.* ; Winkelmann, J. ; Plazzi, G.* ; Nevsimalova, S.* ; Hong, SC.* ; Honda, Y.* ; Honda, M.* ; Högl, B.* ; Ton, TG.* ; Montplaisir, J.* ; Bourgin, P.* ; Kemlink, D.* ; Huang, YS.* ; Warby, S.* ; Einen, M.* ; Eshragh, J.L.* ; Miyagawa, T.* ; Desautels, A.* ; Ruppert, E.* ; Hesla, P.E.* ; Poli, F.* ; Pizza, F.* ; Frauscher, B.* ; Jeong, JH.* ; Lee, S.P.* ; Strohl, K.P.* ; Longstreth, W.T. Jr.* ; Kvale, M.* ; Dobrovolná, M.* ; Ohayon, M.M.* ; Nepom, G.T.* ; Wichmann, H.-E. ; Rouleau, G.A.* ; Gieger, C.* ; Levinson, D.F.* ; Gejman, P.V.* ; Meitinger, T. ; Peppard, P.* ; Young, T.* ; Jennum, P.* ; Steinman, L.* ; Tokunaga, K.* ; Kwok, P.Y.* ; Risch, N.* ; Hallmayer, J.* ; Mignot, E.*

Common variants in P2RY11 are associated with narcolepsy.

Nat. Genet. 43, 66-71 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor subtype P2Y(11) gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10(-10), odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele is correlated with reduced expression of P2RY11 in CD8(+) T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords no keywords
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 43, Issue: 1, Pages: 66-71 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)