Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways

Nair, Rajan P.; Duffin, Kristina Callis; Helms, Cynthia; Ding, Jun; Stuart, Philip E.; Goldgar, David E.; Guðjónsson, Jóhann E.; Li, Yun; Tejasvi, Trilokraj; Feng, Bing‐Jian; Ruether, Andreas; Schreiber, Stefan; Weichenthal, Michael; Gladman, Dafna D.; Rahman, Proton; Schrodi, Steven J; Prahalad, Sampath; Guthery, Stephen L.; Fischer, Judith; Liao, Wilson; Kwok, Pui‐Yan; Menter, Alan; Lathrop, G.M.; Wise, Carol A.; Begovich, Ann B.; Voorhees, John J.; Elder, James T.; Krueger, Gerald G.; Bowcock, Anne M.; Abecasis, Gonçalo R.

doi:10.1038/ng.311

Cited by 1,224 publications

(1,180 citation statements)

References 31 publications

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“…Recently, a genome-wide association scan fo 1,409 psoriasis patients and 1,436 controls revealed a strong association of psoriasis with single nucleotide polymorphisms in loci including ABIN-1 and A20 [68]. Moreover, this study also revealed altered expression of ABIN-1 in the skin of psoriasis patients, indicating that changes in the expression of ABIN-1 may be a key event in the initiation and progression of psoriasis.…”

Section: Abins In Diseasementioning

confidence: 53%

ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling

Verstrepen¹,

Carpentier²,

Verhelst³

et al. 2009

Biochemical Pharmacology

157

126

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ABINs have been described as three different proteins (ABIN-1, ABIN-2, that bind the ubiquitin-editing nuclear factor-B (NF-B) inhibitor protein A20 and which show limited sequence homology. Overexpression of ABINs inhibits NF-B activation by tumor necrosis factor (TNF) and several other stimuli. Similar to A20, ABIN-1 and ABIN-3 expression is NF-B dependent, implicating a potential role for the A20/ABIN complex in the

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Section: Abins In Diseasementioning

confidence: 53%

ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling

Verstrepen¹,

Carpentier²,

Verhelst³

et al. 2009

Biochemical Pharmacology

157

126

View full text Add to dashboard Cite

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“…2 Genome-wide linkage scans have unambiguously mapped a primary disease susceptibility locus (PSORS1) to the major histocompatibility complex (MHC), 3 where refinement studies and resequencing efforts point to HLA-C as the most likely PSORS1 candidate. 4,5 More recently, the advent of genome-wide association scans has allowed the identification of several non-MHC susceptibility genes, including IL12B, IL23R, RNF114, TNFAIP3, TNIP1, IL4/IL13 and LCE3B/3C [6][7][8][9][10][11] Of these, IL12B and IL23R harbour variants that also confer susceptibility to Crohn's disease (CD) 12 and ankylosing spondylitis. 13 Similarly, TNFAIP3 alleles have been associated with rheumatoid arthritis, 14 systemic lupus erythematosus 15 and type I diabetes.…”

Section: Introductionmentioning

confidence: 99%

Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes

et al. 2009

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Psoriasis is an immune-mediated skin disorder, which is inherited as a complex trait. Genome-wide linkage and association studies have identified a major disease susceptibility locus on chromosome 6p21, as well as a number of genetic determinants of smaller effect. Our group has also documented a significant association between psoriasis and CDKAL1, a gene previously implicated in the pathogenesis of Crohn's disease (CD) and type II diabetes (TIID). With this study, we validate this association, through the analysis of CDKAL1 single nucleotide polymorphism (SNP) rs6908425 in an independently ascertained psoriasis dataset (replication sample: 1323 cases vs 1368 controls, P ¼ 0.00012, odds ratio (OR): 1.28; combined sample: 2579 cases vs 4306 controls, P ¼ 4 Â 10 À6 , OR: 1.26). We also show that the association with psoriasis and CD is completely independent from that with TIID. Finally, we report the results of expression studies demonstrating that CDKAL1 transcripts are virtually absent from skin keratinocytes, but are abundantly expressed in immune cells, especially in CD4 þ and CD19 þ lymphocytes. It is to be noted that our data indicate that CDKAL1 becomes markedly downregulated when immune cells are activated with proliferating signals. Taken together, our results document the presence of allelic heterogeneity at the CDKAL1 locus and suggest that CDKAL1 alleles may confer susceptibility to clinically distinct disorders through differential effects on diseasespecific cell types.

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“…The findings of these studies implicated different pathways; one highlighted the involvement of IL23 and nuclear factor-kB pathways, whereas the other study indicated the importance of epidermal differentiation process in the patho-physiology of psoriasis. 143,144 In any case, it is of merit to conduct GWAS in different populations for the same disease to examine the extent of population genetic heterogeneity.…”

Section: Extending Gwas To Different Populationsmentioning

confidence: 99%

The pursuit of genome-wide association studies: where are we now?

et al. 2010

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It is now 5 years since the first genome-wide association studies (GWAS), published in 2005, identified a common risk allele with large effect size for age-related macular degeneration in a small sample set. Following this exciting finding, researchers have become optimistic about the prospect of the genome-wide association approach. However, most of the risk alleles identified in the subsequent GWAS for various complex diseases are common with small effect sizes (odds ratio o1.5). So far, more than 450 GWAS have been published and the associations of greater than 2000 single nucleotide polymorphisms (SNPs) or genetic loci were reported. The aim of this review paper is to give an overview of the evolving field of GWAS, discuss the progress that has been made by GWAS and some of the interesting findings, and summarize what we have learned over the past 5 years about the genetic basis of human complex diseases. This review will focus on GWAS of SNPs association for complex diseases but not studies of copy number variations.

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Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways

Cited by 1,224 publications

References 31 publications

ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling

ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling

Differential contribution of CDKAL1 variants to psoriasis, Crohn's disease and type II diabetes

The pursuit of genome-wide association studies: where are we now?

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