Kornum, BR; Kawashima, M; Faraco, J; Lin, L; Rico, TJ; Hesselson, S; Axtell, RC; Kuipers, H; Weiner, K; Hamacher, A; Kassack, MU; 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, JL; Miyagawa, T; Desautels, A; Ruppert, E; Hesla, PE; Poli, F; Pizza, F; Frauscher, B; Jeong, JH; Lee, SP; Strohl, KP; Longstreth, WT; Kvale, M; Dobrovolná, M; Ohayon, MM; Nepom, GT; Wichmann, HE; Rouleau, GA; Gieger, C; Levinson, DF; Gejman, PV; Meitinger, T; Peppard, P; Young, T; Jennum, P; Steinman, L; Tokunaga, K; Kwok, PY; Risch, N; Hallmayer, J; Mignot, E     «

Kornum, BR; Kawashima, M; Faraco, J; Lin, L; Rico, TJ; Hesselson, S; Axtell, RC; Kuipers, H; Weiner, K; Hamacher, A; Kassack, MU; 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, JL; Miyagawa, T; Desautels, A; Ruppert, E; Hesla, PE; Poli, F; Pizza, F; Frauscher, B; Jeong, JH; Lee, SP; Strohl, KP; Longstreth, WT; Kvale, M; Dobrovolná, M; Ohay...     »

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?? gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10?¹?, 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.     «

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?? gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 × 10?¹?, odds ratio = 1.28,...     »