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Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease 总被引:2,自引:0,他引:2
Barrett JC Hansoul S Nicolae DL Cho JH Duerr RH Rioux JD Brant SR Silverberg MS Taylor KD Barmada MM Bitton A Dassopoulos T Datta LW Green T Griffiths AM Kistner EO Murtha MT Regueiro MD Rotter JI Schumm LP Steinhart AH Targan SR Xavier RJ;NIDDK IBD Genetics Consortium Libioulle C Sandor C Lathrop M Belaiche J Dewit O Gut I Heath S Laukens D Mni M Rutgeerts P Van Gossum A Zelenika D Franchimont D Hugot JP de Vos M Vermeire S 《Nature genetics》2008,40(8):955-962
Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development. 相似文献
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Rioux JD Xavier RJ Taylor KD Silverberg MS Goyette P Huett A Green T Kuballa P Barmada MM Datta LW Shugart YY Griffiths AM Targan SR Ippoliti AF Bernard EJ Mei L Nicolae DL Regueiro M Schumm LP Steinhart AH Rotter JI Duerr RH Cho JH Daly MJ Brant SR 《Nature genetics》2007,39(5):596-604
We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease. 相似文献
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碲锡铅(Pb1-xSnxTe)是一种禁带宽度可调的三元化合物半导体,用它不仅可制备814μm的高灵敏度的红外探测器,而且可以制备长波红外可调谐激光器. 相似文献
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