Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.
paper
Cited
Public
- Authors
- Silverberg, Mark S; Cho, Judy H; Rioux, John D; McGovern, Dermot P B; 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 F; Lahaie, Raymond G; Latiano, Anna; ParΓ©, Pierre; Proctor, Deborah D; Regueiro, Miguel D; 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
- Year
- 2009
- Journal
- Nature genetics
- PMID
- 19122664
- DOI
- 10.1038/ng.275
- PMCID
- PMC2652837
Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29).
Association signals and recombination rates for loci demonstrating genome-wide significant association with UC on chromosomes a) 1p36, b) 1p31, c) 6p21 and d) 12q15. The vertical axis scale on the left side of each plot represents the βlog10 of the P values. The vertical axis scale on the right side of each plot represents the recombination rate in cM/Mb. The UC GWAS βlog10 GEM P values are plotted as small diamonds (all arrays shared SNPs GEM dataset, see Supplementary Table 1 online) and small circles (HumanHap550 only SNPs GEM dataset, see Supplementary Table 1 online). Linkage disequilibrium (r2) in the GWAS control data to the single most significantly associated regional SNP is color-coded (red: r2 greater than 0.8; orange: r2 0.5β0.8; yellow: r2 0.2β0.5; white: r2 less than 0.2). Large blue diamonds with corresponding rs number and P value labels represent combined UC GWAS and replication case-control significance estimates. Light blue lines represent the recombination rates. Conditional analyses (see Supplementary Table 3 online) of replicated markers (large blue diamonds) suggest the presence of independent association signals on chromosome 1p36 and on chromosome 12q15 separated by recombination hotspots.
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