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Common variants in P2RY11 are associated with narcolepsy.

  • Author(s): Kornum, Birgitte R
  • Kawashima, Minae
  • Faraco, Juliette
  • Lin, Ling
  • Rico, Thomas J
  • Hesselson, Stephanie
  • Axtell, Robert C
  • Kuipers, Hedwich
  • Weiner, Karin
  • Hamacher, Alexandra
  • Kassack, Matthias U
  • Han, Fang
  • Knudsen, Stine
  • Li, Jing
  • Dong, Xiaosong
  • Winkelmann, Juliane
  • Plazzi, Giuseppe
  • Nevsimalova, Sona
  • Hong, Seung-Chul
  • Honda, Yutaka
  • Honda, Makoto
  • Högl, Birgit
  • Ton, Thanh GN
  • Montplaisir, Jacques
  • Bourgin, Patrice
  • Kemlink, David
  • Huang, Yu-Shu
  • Warby, Simon
  • Einen, Mali
  • Eshragh, Jasmin L
  • Miyagawa, Taku
  • Desautels, Alex
  • Ruppert, Elisabeth
  • Hesla, Per Egil
  • Poli, Francesca
  • Pizza, Fabio
  • Frauscher, Birgit
  • Jeong, Jong-Hyun
  • Lee, Sung-Pil
  • Strohl, Kingman P
  • Longstreth, William T
  • Kvale, Mark
  • Dobrovolna, Marie
  • Ohayon, Maurice M
  • Nepom, Gerald T
  • Wichmann, H-Erich
  • Rouleau, Guy A
  • Gieger, Christian
  • Levinson, Douglas F
  • Gejman, Pablo V
  • Meitinger, Thomas
  • Peppard, Paul
  • Young, Terry
  • Jennum, Poul
  • Steinman, Lawrence
  • Tokunaga, Katsushi
  • Kwok, Pui-Yan
  • Risch, Neil
  • Hallmayer, Joachim
  • Mignot, Emmanuel
  • et al.

Published Web Location

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 P2Y₁₁ 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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