Ulcerative colitis–risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study

Silverberg, Mark S.; Cho, Judy H.; Rioux, John D.; McGovern, Dermot; Wu, Jing; Annese, Vito; Achkar, Jean Paul; Goyette, Philippe; Scott, Regan; Xu, Wei; Barmada, M. Michael; Klei, Lambertus; Daly, Mark J.; Abraham, Clara; Bayless, Theodore M.; Bossa, Fabrizio; Griffiths, Anne M.; Ippoliti, Andrew; Lahaie, Raymond G.; Latiano, Anna; Paré, Pierre; Proctor, Deborah D.; Regueiro, Miguel; Steinhart, A. Hillary; Targan, Stephan R.; Schumm, L. Philip; Kistner, Emily O.; Lee, Annette T.; Gregersen, Peter K.; Rotter, Jerome I.; Brant, Steven R.; Taylor, Kent D.; Roeder, Kathryn; Duerr, Richard H.

doi:10.1038/ng.275

Cited by 367 publications

(291 citation statements)

References 28 publications

(49 reference statements)

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“…5,6 Of the two types of IBD, the genetic contribution to disease risk has been documented more extensively and clearly for CD [7][8][9][10][11][12][13][14][15][16][17] than for UC. [18][19][20][21] So far, linkage and genome-wide association studies have identified more than 30 CD-susceptibility loci in Caucasian populations. 22 Of those, NOD2, ATG16L1 and IRGM were CD specific, whereas genes involved in Th17 differentiation, including IL23R, IL12B, JAK2, STAT3 and TNFSF15 were shared between UC and CD in Caucasians.…”

Section: Introductionmentioning

confidence: 99%

No association between TNFSF15 and IL23R with ulcerative colitis in Koreans

et al. 2011

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Recent genome-wide association studies have shown that some Crohn's disease (CD)-associated loci also contribute to ulcerative colitis (UC) susceptibility. To understand the genetic relationship between the two forms of inflammatory bowel disease, we investigated the well-established CD-susceptibility genes TNFSF15 (tumor necrosis factor ligand superfamily, member 15) and IL23R in Korean patients with UC. Eight TNFSF15 and five IL23R single-nucleotide polymorphisms were genotyped in 654 patients with UC and in 601 healthy controls. There was no association between TNFSF15 or IL23R variants and UC in Korean individuals, in contrast to previous reports of a shared association of the IL23R gene with both CD and UC in Caucasian individuals. Our data suggest that neither TNFSF15 nor IL23R variants contribute to UC susceptibility in Koreans.

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Section: Introductionmentioning

confidence: 99%

No association between TNFSF15 and IL23R with ulcerative colitis in Koreans

et al. 2011

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“…NOD2, the first gene linked with increased susceptibility to CD, has later been shown to be associated with ileal disease, early age of onset, stricturing, and/or penetrating phenotype and increased need for surgery [5,9,10,[38][39][40][41][42][43][44][45][46][47][48][49]. Among the UC susceptibility genes, HLA DRB1*0103 and the multidrug resistance gene 1 (MDR1/ABCB1) were also identified as being associated with extensive and severe disease [17,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…Among the UC susceptibility genes, HLA DRB1*0103 and the multidrug resistance gene 1 (MDR1/ABCB1) also contribute to clinical phenotype and natural history, being associated with extensive and severe disease [17,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. In CD, NOD2 gene mutations have repeatedly been shown to be associated with ileal disease, early age of onset, stricturing, and/or penetrating phenotype and increased need for surgery [5,9,10,[38][39][40][41][42][43][44][45][46][47][48][49].…”

Section: Introductionmentioning

confidence: 99%

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

Freire

Cardoso

Figueiredo

et al. 2014

Int J Colorectal Dis

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Purpose NOD2 mutations have been linked to an increased risk of Crohn's disease and to some of its phenotypes. The association between NOD2 mutations and susceptibility to ulcerative colitis (UC) remains somewhat controversial and potential correlations between these mutations and UC phenotype have not been studied. Aim To assess whether NOD2 mutations are a risk factor for UC in Portugal and if there are any genotype-phenotype correlations in these patients. Methods The three main NOD2 mutations were searched in 200 patients with UC and in 202 healthy controls. Results NOD2 mutations were present in 28 patients with UC (14.0 %) and in 27 controls (13.4 %) (p=0.853). Mutation carriers were more likely to receive steroids during the first year of disease than non-carriers (54.2 % vs. 29.6 %, p= 0.018) and among these patients the need for intravenous administration was more frequent in those with the R702W polymorphism (90.0 % vs. 45.5 %, p=0.014). In patients with severe colitis admitted for intravenous steroids, a greater proportion of mutation carriers was considered intravenous-steroid refractory and required salvage therapy (90.0 % vs. 38.1 %, p=0.004). Patients with NOD2 mutation were submitted to colectomy more frequently than non-carriers (17.9 % vs. 4.1 %. p=0.015). No correlation with the need for immunosuppressants/immunomodulators was found. Conclusions In the Portuguese population, NOD2 mutations do not increase the risk of UC but are associated with a more aggressive course including greater need of steroids in the first

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“…Novel susceptibility loci have been identified for UC in Japanese population 109 but they were not detected in the other three GWAS conducted in Europeans. [110][111][112] Attempts to dissect the genetic basis of early-onset or pediatric-onset IBD have also yielded some success, where several previously unreported regions for IBD have been identified. [113][114] In addition, the GWAS also found associations of many loci previously implicated for adult-onset CD and UC with early-onset IBD, thus for the first time suggesting a close relationship in the patho-physiology between early-and adult-onset IBD.…”

Section: The Recent 2 Years: 2008 and 2009mentioning

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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Ulcerative colitis–risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study

Cited by 367 publications

References 28 publications

No association between TNFSF15 and IL23R with ulcerative colitis in Koreans

No association between TNFSF15 and IL23R with ulcerative colitis in Koreans

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

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

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