Laboratory for Genotyping Development, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Gastroenterology. 2013 Apr;144(4):781-8. doi: 10.1053/j.gastro.2012.12.021. Epub 2012 Dec 22.
BACKGROUND & AIMS: Crohn's disease is an inflammatory bowel disease induced by multiple genetic and environmental factors. Genome-wide association studies have identified genetic factors that affect the risk for Crohn's disease in European populations, but information from other ethnic groups is scarce. We therefore investigated genetic factors associated with Crohn's disease in the Japanese population.
We performed a genome-wide association study with 372 individuals with Crohn's disease (cases) and 3389 controls, all from the Japanese population. To confirm identified associations, we performed a replication study with an independent panel of 1151 Crohn's disease cases and 15,800 controls. We also performed an association analysis using genome-wide genotype imputation in the discovery cohort.
We confirmed associations of Crohn's disease with variants in MHC (rs7765379, P = 2.11 × 10(-59)), TNFSF15 (rs6478106, P = 3.87 × 10(-45)), and STAT3 (rs9891119, P = 2.24 × 10(-14)). We identified 2 new susceptibility loci: on chromosome 4p14 (rs1487630, P = 2.40 × 10(-11); odds ratio, 1.33), and in the SLC25A15-ELF1-WBP4 region on 13q14 (rs7329174 in ELF1, P = 5.12 × 10(-9); odds ratio, 1.27).
In a genome-wide association study, we identified 2 new susceptibility loci for Crohn's disease in a Japanese population. These findings could increase our understanding of the pathogenesis of Crohn's disease.
克罗恩病是一种由多种遗传和环境因素引起的炎症性肠病。全基因组关联研究已经确定了影响欧洲人群克罗恩病风险的遗传因素,但来自其他种族群体的信息很少。因此,我们研究了日本人群中与克罗恩病相关的遗传因素。
我们对来自日本人群的 372 名克罗恩病患者(病例)和 3389 名对照进行了全基因组关联研究。为了确认鉴定出的关联,我们使用独立的 1151 名克罗恩病病例和 15800 名对照的验证队列进行了重复研究。我们还在发现队列中使用全基因组基因型推断进行了关联分析。
我们证实了克罗恩病与 MHC 中的变体(rs7765379,P=2.11×10(-59))、TNFSF15(rs6478106,P=3.87×10(-45))和 STAT3(rs9891119,P=2.24×10(-14))之间的关联。我们确定了 2 个新的易感位点:位于染色体 4p14(rs1487630,P=2.40×10(-11);优势比,1.33)和 13q14 上的 SLC25A15-ELF1-WBP4 区域(ELF1 中的 rs7329174,P=5.12×10(-9);优势比,1.27)。
在全基因组关联研究中,我们在日本人群中发现了克罗恩病的 2 个新的易感位点。这些发现可以提高我们对克罗恩病发病机制的理解。