Common variants in P2RY11 are associated with narcolepsy
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Common variants in P2RY11 are associated with narcolepsy. / 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 G N; 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; Jennum, Poul.
In: Nature Genetics, Vol. 43, No. 1, 01.2011, p. 66-71.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Common variants in P2RY11 are associated with narcolepsy
AU - Kornum, Birgitte R
AU - Kawashima, Minae
AU - Faraco, Juliette
AU - Lin, Ling
AU - Rico, Thomas J
AU - Hesselson, Stephanie
AU - Axtell, Robert C
AU - Kuipers, Hedwich
AU - Weiner, Karin
AU - Hamacher, Alexandra
AU - Kassack, Matthias U
AU - Han, Fang
AU - Knudsen, Stine
AU - Li, Jing
AU - Dong, Xiaosong
AU - Winkelmann, Juliane
AU - Plazzi, Giuseppe
AU - Nevsimalova, Sona
AU - Hong, Seung-Chul
AU - Honda, Yutaka
AU - Honda, Makoto
AU - Högl, Birgit
AU - Ton, Thanh G N
AU - Montplaisir, Jacques
AU - Bourgin, Patrice
AU - Kemlink, David
AU - Huang, Yu-Shu
AU - Warby, Simon
AU - Einen, Mali
AU - Eshragh, Jasmin L
AU - Miyagawa, Taku
AU - Desautels, Alex
AU - Ruppert, Elisabeth
AU - Hesla, Per Egil
AU - Poli, Francesca
AU - Pizza, Fabio
AU - Frauscher, Birgit
AU - Jeong, Jong-Hyun
AU - Lee, Sung-Pil
AU - Strohl, Kingman P
AU - Longstreth, William T
AU - Kvale, Mark
AU - Dobrovolna, Marie
AU - Ohayon, Maurice M
AU - Nepom, Gerald T
AU - Wichmann, H-Erich
AU - Rouleau, Guy A
AU - Gieger, Christian
AU - Levinson, Douglas F
AU - Jennum, Poul
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - African Americans
KW - Alleles
KW - Asian Continental Ancestry Group
KW - Case-Control Studies
KW - Ethnic Groups/genetics
KW - European Continental Ancestry Group
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Humans
KW - Narcolepsy/genetics
KW - Odds Ratio
KW - Polymorphism, Single Nucleotide
KW - Receptors, Purinergic P2/genetics
U2 - 10.1038/ng.734
DO - 10.1038/ng.734
M3 - Journal article
C2 - 21170044
VL - 43
SP - 66
EP - 71
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 1
ER -
ID: 196168888