Common variants in P2RY11 are associated with narcolepsy

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

Research output: Contribution to journalArticlepeer-review


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 3ĝ€2 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 1.19ĝ€"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.

Original languageEnglish
Pages (from-to)66-71
Number of pages6
JournalNature Genetics
Issue number1
Publication statusPublished - Jan 2011

ASJC Scopus subject areas

  • Genetics


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