DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Narcolepsy with cataplexy. The EFO term narcolepsy with cataplexy was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: narcolepsy with cataplexy

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

H Toyoda, T Miyagawa, A Koike, T Kanbayashi, A Imanishi, Y Sagawa, N Kotorii, T Kotorii, Y Hashizume, K Ogi, H Hiejima, Y Kamei, A Hida, M Miyamoto, M Imai, Y Fujimura, Y Tamura, A Ikegami, Y Wada, S Moriya, H Furuya, M Takeuchi, Y Kirino, A Meguro, EF Remmers, Y Kawamura, T Otowa, A Miyashita, K Kashiwase, SS Khor, M Yamasaki, R Kuwano, T Sasaki, J Ishigooka, K Kuroda, K Kume, S Chiba, N Yamada, M Okawa, K Hirata, N Mizuki, N Uchimura, T Shimizu, Y Inoue, Y Honda, K Mishima, M Honda, K Tokunaga

TITLE:

A polymorphism in CCR1/CCR3 is associated with narcolepsy.

JOURNAL:

Brain, behavior, and immunity Oct 2015, Vol 49, pp. 148-55

ABSTRACT:

Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function. PUBMED: 25986216
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