Common variants in P2RY11 are associated with narcolepsy
Research output: Contribution to journal › Journal article › Research › peer-review
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 Honda & 30 others
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.
|Number of pages||6|
|Publication status||Published - Jan 2011|
- African Americans, Alleles, Asian Continental Ancestry Group, Case-Control Studies, Ethnic Groups/genetics, European Continental Ancestry Group, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Narcolepsy/genetics, Odds Ratio, Polymorphism, Single Nucleotide, Receptors, Purinergic P2/genetics