rs1154155 - TRAJ10 - TRAJ9

Magnitude 4.5 · 6 studies on file

Reported associations

• A polymorphism in CCR1/CCR3 is associated with narcolepsy. - Brain, behavior, and immunity (2016) · Toyoda H, Miyagawa T, Koike A, Kanbayashi T, Imanishi A, Sagawa Y, Kotorii N, Kotorii T, Hashizume Y, Ogi K, Hiejima H, Kamei Y, Hida A, Miyamoto M, Imai M, Fujimura Y, Tamura Y, Ikegami A, Wada Y, Moriya S, Furuya H, Takeuchi M, Kirino Y, Meguro A, Remmers EF, Kawamura Y, Otowa T, Miyashita A, Kashiwase K, Khor SS, Yamasaki M, Kuwano R, Sasaki T, Ishigooka J, Kuroda K, Kume K, Chiba S, Yamada N, Okawa M, Hirata K, Mizuki N, Uchimura N, Shimizu T, Inoue Y, Honda Y, Mishima K, Honda M, Tokunaga K · PubMed 25986216

  Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB115:01-DQB106:02 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),

• Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. - Nature genetics (2010) · Hor H, Kutalik Z, Dauvilliers Y, Valsesia A, Lammers GJ, Donjacour CE, Iranzo A, Santamaria J, Peraita Adrados R, Vicario JL, Overeem S, Arnulf I, Theodorou I, Jennum P, Knudsen S, Bassetti C, Mathis J, Lecendreux M, Mayer G, Geisler P, Benetó A, Petit B, Pfister C, Bürki JV, Didelot G, Billiard M, Ercilla G, Verduijn W, Claas FH, Vollenweider P, Waeber G, Waterworth DM, Mooser V, Heinzer R, Beckmann JS, Bergmann S, Tafti M · PubMed 20711174

  Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB11501-DQB10602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing narcolepsy. To further define the genetic basis of narcolepsy risk, we performed a genome-wide association study (GWAS) in 562 European individuals with narcolepsy (cases) and 702 ethnically matched controls, with independent replication in 370 cases and 495 controls, all heterozygous for DRB11501-DQB10602. We found association with a protective variant near HLA-DQA2 (rs2858884; P < 3 x 10(-8)). Further analysis revealed that rs2858884 is strongly linked to DRB103-DQB102 (P < 4 x 10(-43)) and D

• ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy - Unknown journal (n.d.) · Unknown authors · PubMed 23459209

  ABSTRACT: Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome

• Genome Wide Analysis of Narcolepsy in China Implicates Novel Immune Loci and Reveals Changes in Association Prior to Versus After the 2009 H1N1 Influenza Pandemic - Unknown journal (n.d.) · Unknown authors · PubMed 24204295

  ABSTRACT: Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7×10−9 OR 0.77), ZNF365 (rs10995245 max P = 1.2×10−11 OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2×10−9 OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10−9 beta −1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 

• Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy - Unknown journal (n.d.) · Unknown authors · PubMed 37188663

  ABSTRACT: Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB103:01 and DPB104:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB106:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ24, TRAJ28 and TRBV4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be

• Narcolepsy is strongly associated with the TCR alpha locus - Unknown journal (n.d.) · Unknown authors · PubMed 19412176

  [INTRO] Narcolepsy-cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals. Narcolepsy was first shown to be tightly associated with HLA-DR2, and later sublocalized to DQB1*0602. Following studies in dogs and mice, a 95% loss of hypocretin-producing cells in human postmortem hypothalami was reported, Using Genome Wide Association (GWA) in Caucasians with replication in three ethnic groups, we found association with polymorphisms in the T-Cell receptor alpha (TCRA) locus, with highest significance at rs1154155 (average allelic odds ratio 1.69, genotype odds ratios 1.94 and 2.55, p<10−21, 1830 cases, 2164 controls). This is the first documented genetic involvement of the TCRA locus, the major receptor for HLA-peptide presentation, in any diseas

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