Association Study of 71 European Crohn's Disease Susceptibility Loci in a Japanese Population
Association Study of 71 European Crohn's Disease Susceptibility Loci in a Japanese Population
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DOI：
10.1097/mib.0b013e31828075e7
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发表时间：
2013-03-01
影响因子：
4.9
通讯作者：
Kubo, Michiaki
中科院分区：
文献类型：
--
作者：
Hirano, Atsushi;Yamazaki, Keiko;Kubo, Michiaki
背景：一项对一系列欧洲全基因组关联研究的大规模荟萃分析揭示了71个克罗恩病(CD)的易感基因。方法：采用Cochran-Armitage趋势检验方法，对1311例CD患者和6585例日本血统对照的71个单核苷酸多态(SNPs)进行基因分型，并分析其与CD的相关性。结果：2 7个SNPs至少存在名义上的关联(P<；0.0 5)，其中11个在Bonferroni校正后仍然显著(P<；0.0007)。尽管有很高的统计能力，但我们在17个座位上找不到任何关联。此外，9个基因座的SNPs在日本人群中很少见或缺失。在日本人群中，涉及先天免疫系统的遗传变异(NOD2、ATG16L1和IRGM)与CD易感性无关。基因-表型分析显示，TNFSF15的一个标记rs3810936与严重的CD表型相关。结论：本研究提示日本和欧洲人群存在不同的CD易感性遗传背景。(炎症性肠病2013；19：526-533)
Background: A large-scale meta-analysis of a series of European genome-wide association studies revealed 71 susceptibility loci for Crohn's disease (CD). However, it is not clear whether these susceptibility loci are also shared with Japanese populations.Methods: We genotyped 71 single-nucleotide polymorphisms (SNPs) comprising 1311 CD cases and 6585 controls of Japanese descent, and their associations with CD were evaluated using the Cochran-Armitage trend test. In addition, genotype-phenotype analyses were conducted on the SNPs showing associations with Japanese CD based on the Montreal classification.Results: Twenty-seven SNPs showed at least nominal association (P < 0.05) and 11 of them remained significant even after Bonferroni correction (P < 0.0007). Despite high statistical power, we could not find any association in 17 loci. Moreover, SNPs in 9 loci were rare or absent in the Japanese population. Genetic variations involved in the innate immune system (NOD2, ATG16L1, and IRGM) showed no association with CD susceptibility in the Japanese population. Genotype-phenotype analyses showed that rs3810936, a marker of TNFSF15, correlated with severe CD phenotypes.Conclusions: Our study suggests that there is a differential genetic background of CD susceptibility between Japanese and European populations. (Inflamm Bowel Dis 2013;19:526-533)