Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10?1? and P = 4.1 × 10??, respectively).     

Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility

Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls. Twenty of the most significantly associated SNPs were tested for replication in three independent European case-control panels comprising a total of 1,855 individuals with UC and 3,091 controls. Among the four consistently replicated markers, SNP rs3024505 immediately flanking the IL10 (interleukin 10) gene on chromosome 1q32.1 showed the most significant association in the combined verification samples (P = 1.35 x 10(-12); OR = 1.46 (1.31-1.62)). The other markers were located in ARPC2 and in the HLA-BTNL2 region. Association between rs3024505 and CD (1,848 cases, 1,804 controls) was weak (P = 0.013; OR = 1.17 (1.01-1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD.     

硅谷：美国高科技发展的标志

美国硅谷的发展在整个世界引起了广泛的兴趣和关注 ,硅谷已成为美国高科技发展的标志 ,任何其他国家和地区的高科技的发展都不能和硅谷相比。经济论坛硅谷位于海湾和山谷之间 ,东西宽１６公里 ,南北跨度５０公里 ,并且正在不断延长。硅谷有４０００家公司 ,他们都很小。８０年代后期 ,ＩＢＭ公司总裁访问了我大学 ,他告诉我硅谷３０００多家公司中只有少于１００家的年收入超过１亿美元。硅谷是从事信息技术的、小的、成长型公司的产地。直到硅半导体芯片运用于微电子工业 ,硅谷才成为美国乃至世界的高科技工业的中心。现在 ,许多大公司将生…