Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan; Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan.
Inflamm Bowel Dis. 2011 Dec;17(12):2407-15. doi: 10.1002/ibd.21651. Epub 2011 Feb 23.
BACKGROUND: Both ulcerative colitis (UC) and Crohn's disease (CD) have a complex etiology involving multiple genetic and environmental factors. Many genome-wide association studies (GWAS) and subsequent replication studies revealed that both diseases share some of the susceptibility loci; however, common genetic factors for both diseases are not fully elucidated. This study is aimed to identify the common genetic factors for CD and UC by a meta-analysis of published studies. METHODS: We first reviewed the 10 GWAS for CD to select candidate single nucleotide polymorphisms (SNPs). Next, we performed a PubMed literature search up to June 30, 2010 and carried out a systemic review of published studies that examined the association of CD susceptibility loci in UC patients. Meta-analysis was carried out using the inverse variance-weighted method or the DerSimonian-Laird method after estimating the heterogeneity among the studies. The data for highly linked SNPs were combined. Finally, we performed a meta-analysis of 43 published studies in 45 SNPs located at 33 loci by using a total of 4852 to 31,125 subjects. RESULTS: We confirmed the association of 17 reported common susceptibility loci. Moreover, we found associations at eight additional loci: GCKR, ATG16L1, CDKAL1, ZNF365, LRRK2-MUC19, C13orf31, PTPN2, and SBNO2. The genetic risk of each locus was modest (odds ratios ranged from 1.05-1.22) except IL23R. CONCLUSIONS: These results indicate that CD and UC share many susceptibility loci with small genetic effect. Our data provide further understanding of the common pathogenesis between CD and UC.
背景:溃疡性结肠炎(UC)和克罗恩病(CD)的病因均十分复杂,涉及多种遗传和环境因素。许多全基因组关联研究(GWAS)和后续的复制研究表明,这两种疾病具有一些共同的易感基因座;然而,这两种疾病的常见遗传因素尚未完全阐明。本研究旨在通过对已发表研究的荟萃分析,确定 CD 和 UC 的共同遗传因素。
方法:我们首先回顾了 10 项 CD 的 GWAS 研究,以选择候选单核苷酸多态性(SNP)。接下来,我们进行了文献检索,截至 2010 年 6 月 30 日,对已发表的研究进行了系统性综述,这些研究检查了 UC 患者 CD 易感性基因座的相关性。使用异质性估计后,采用逆方差加权法或德西蒙尼-劳尔德法进行荟萃分析。对高度连锁的 SNP 数据进行了合并。最后,我们对 33 个基因座的 43 项已发表研究的 45 个 SNP 进行了荟萃分析,共纳入 4852 至 31125 例患者。
结果:我们证实了 17 个已报道的常见易感性基因座的相关性。此外,我们还发现了另外 8 个基因座的相关性:GCKR、ATG16L1、CDKAL1、ZNF365、LRRK2-MUC19、C13orf31、PTPN2 和 SBNO2。除 IL23R 外,每个基因座的遗传风险均较小(比值比范围为 1.05-1.22)。
结论:这些结果表明,CD 和 UC 具有许多具有较小遗传效应的共同易感基因座。我们的数据进一步加深了对 CD 和 UC 之间共同发病机制的理解。
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