排序方式: 共有2条查询结果,搜索用时 46 毫秒
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Kugathasan S Baldassano RN Bradfield JP Sleiman PM Imielinski M Guthery SL Cucchiara S Kim CE Frackelton EC Annaiah K Glessner JT Santa E Willson T Eckert AW Bonkowski E Shaner JL Smith RM Otieno FG Peterson N Abrams DJ Chiavacci RM Grundmeier R Mamula P Tomer G Piccoli DA Monos DS Annese V Denson LA Grant SF Hakonarson H 《Nature genetics》2008,40(10):1211-1215
Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 x 10(-8) and 6.95 x 10(-8), respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 x 10(-8); OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively. 相似文献
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Anderson CA Boucher G Lees CW Franke A D'Amato M Taylor KD Lee JC Goyette P Imielinski M Latiano A Lagacé C Scott R Amininejad L Bumpstead S Baidoo L Baldassano RN Barclay M Bayless TM Brand S Büning C Colombel JF Denson LA De Vos M Dubinsky M Edwards C Ellinghaus D Fehrmann RS Floyd JA Florin T Franchimont D Franke L Georges M Glas J Glazer NL Guthery SL Haritunians T Hayward NK Hugot JP Jobin G Laukens D Lawrance I Lémann M Levine A Libioulle C Louis E McGovern DP Milla M Montgomery GW 《Nature genetics》2011,43(3):246-252
Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis. 相似文献
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