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.
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.
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.
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.
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.
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。
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。
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）。
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。
