Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2

Ellinghaus, Eva; Ellinghaus, David; Stuart, Philip E.; Nair, Rajan P.; Debrus, Sophie; Raelson, John; Belouchi, Majid; Fournier, Hélène; Reinhard, Claudia; Ding, Jun; Li, Yun; Tejasvi, Trilokraj; Gudjonsson, Sigurjon A.; Stoll, Stefan; Voorhees, John J.; Lambert, Sylviane; Weidinger, Stephan; Eberlein, Bernadette; Kunz, Manfred; Rahman, Proton; Gladman, Dafna D.; Gieger, Christian; Wichmann, H‐Erich; Karlsen, Tom H.; Mayr, Gabriele; Albrecht, Mario; Kabelitz, Dieter; Mrowietz, Ulrich; Abecasis, Gonçalo R.; Elder, James T.; Schreiber, Stefan; Weichenthal, Michael; Franke, André

doi:10.1038/ng.689

Cited by 326 publications

(287 citation statements)

References 38 publications

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“…Although none of these SNPs have been associated with RA in other studies, rs2522056 has been associated with Crohn's disease (42), an increase in acute phase response (43) and fibrinogen levels and, therefore, can be considered a risk factor for cardiovascular disease (44). The TRAF3IP2 gene has been associated with the risk of developing psoriasis (45) and psoriatic arthritis (46); ICOS, with alopecia areata; KIAA1542, with the presence of anti-dsDNA antibody postivity in systemic lupus erythematosus (47), with the function of the intergenic region between KIAA1919 and REV3L being unknown.…”

Section: R E S E a R C H A R T I C L E M O L M Ementioning

confidence: 96%

Immunochip Identifies Novel, and Replicates Known, Genetic Risk Loci for Rheumatoid Arthritis in Black South Africans

Govind

Choudhury

Hodkinson

et al. 2014

Mol Med

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The aim of this study was to identify genetic variants associated with rheumatoid arthritis (RA) risk in black South Africans. Black South African RA patients (n = 263) were compared with healthy controls (n = 374). Genotyping was performed using the Immunochip, and four-digit high-resolution human leukocyte antigen (HLA) typing was performed by DNA sequencing of exon 2. Standard quality control measures were implemented on the data. The strongest associations were in the intergenic region between the HLA-DRB1 and HLA-DQA1 loci. After conditioning on HLA-DRB1 alleles, the effect in the rest of the extended major histocompatibility (MHC) diminished. Non-HLA single nucleotide polymorphisms (SNPs) in the intergenic regions LOC389203|RBPJ, LOC100131131|IL1R1, KIAA1919|REV3L, LOC643749|TRAF3IP2, and SNPs in the intron and untranslated regions (UTR) of IRF1 and the intronic region of ICOS and KIAA1542 showed association with RA (p < 5 × 10 -5). Of the SNPs previously associated with RA in Caucasians, one SNP, rs874040, locating to the intergenic region LOC389203|RBPJ was replicated in this study. None of the variants in the PTPN22 gene was significantly associated. The seropositive subgroups showed similar results to the overall cohort. The effects observed across the HLA region are most likely due to HLA-DRB1, and secondary effects in the extended MHC cannot be detected. Seven non-HLA loci are associated with RA in black South Africans. Similar to Caucasians, the intergenic region between LOC38920 and RBPJ is associated with RA in this population. The strong association of the R620W variant of the PTPN22 gene with RA in Caucasians was not replicated since this variant was monomorphic in our study, but other SNP variants of the PTPN22 gene were also not associated with RA in black South Africans, suggesting that this locus does not play a major role in RA in this population.

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Section: R E S E a R C H A R T I C L E M O L M Ementioning

confidence: 96%

Immunochip Identifies Novel, and Replicates Known, Genetic Risk Loci for Rheumatoid Arthritis in Black South Africans

Govind

Choudhury

Hodkinson

et al. 2014

Mol Med

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“…Advances in high-throughput genotyping technologies and the completion of the genomewide database of common genetic sequence variation (HapMap project) have paved the way to the identification of a number of psoriasis susceptibility genes by means of GWAS (Capon et al 2008;de Cid et al 2009;Nair et al 2009;Zhang et al 2009;Ellinghaus et al 2010;Huffmeier et al 2010;Strange et al 2010;Stuart et al 2010) and subsequent meta-analysis (Ellinghaus et al 2012a;Tsoi et al 2012). Collectively, these studies identified 36 independent psoriasis-associated regions within individuals of European ancestry (Tsoi et al 2012), plus five more uniquely associated in the Chinese population (Sun et al 2010).…”

Section: Psoriasis Susceptibility Genes Identified By Gwassmentioning

confidence: 99%

Psoriasis

Meglio

Villanova

Nestle

2014

Cold Spring Harbor Perspectives in Medicine

246

183

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Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life.This skin is me, I can't get out.

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“…19,96,97 Similar to IBD, GWAS data from psoriasis specimens show that IL-23R and Act1 are psoriasis-associated genes. [98][99][100] In mice, intracutaneous injection of IL-23 causes psoriasis-like epidermal hyperplasia; this skin inflammation is ameliorated in Il17a-, Il17ra-or Il22-deficient mice. 101,102 The TLR7/8 agonist imiquimod (IMQ) can also induce and exacerbate a psoriasis-like syndrome in mice.…”

Section: Il-17dmentioning

confidence: 99%

The roles and functional mechanisms of interleukin-17 family cytokines in mucosal immunity

et al. 2016

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The mucosal immune system serves as our front-line defense against pathogens. It also tightly maintains immune tolerance to self-symbiotic bacteria, which are usually called commensals. Sensing both types of microorganisms is modulated by signalling primarily through various pattern-recognition receptors (PRRs) on barrier epithelial cells or immune cells. After sensing, proinflammatory molecules such as cytokines are released by these cells to mediate either defensive or tolerant responses. The interleukin-17 (IL-17) family members belong to a newly characterized cytokine subset that is critical for the maintenance of mucosal homeostasis. In this review, we will summarize recent progress on the diverse functions and signals of this family of cytokines at different mucosal edges.

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Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2

Cited by 326 publications

References 38 publications

Immunochip Identifies Novel, and Replicates Known, Genetic Risk Loci for Rheumatoid Arthritis in Black South Africans

Immunochip Identifies Novel, and Replicates Known, Genetic Risk Loci for Rheumatoid Arthritis in Black South Africans

Psoriasis

The roles and functional mechanisms of interleukin-17 family cytokines in mucosal immunity

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