在一项扩展的全基因组关联研究中鉴定韩国人炎症性肠病的三个新的易感基因座。

Identification of Three Novel Susceptibility Loci for Inflammatory Bowel Disease in Koreans in an Extended Genome-Wide Association Study.

机构信息

Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

出版信息

J Crohns Colitis. 2021 Nov 8;15(11):1898-1907. doi: 10.1093/ecco-jcc/jjab060.

DOI:10.1093/ecco-jcc/jjab060

PMID:33853113

Abstract

BACKGROUND AND AIMS

Genome-wide association studies [GWAS] of inflammatory bowel disease [IBD] in multiple populations have identified over 240 susceptibility loci. We previously performed a largest-to-date Asian-specific IBD GWAS to identify two new IBD risk loci and confirm associations with 28 established loci. To identify additional susceptibility loci in Asians, we expanded our previous study design by doubling the case size with an additional dataset of 1726 cases and 378 controls.

METHODS

An inverse-variance fixed-effects meta-analysis was performed between the previous and the new GWAS dataset, comprising a total of 3195 cases and 4419 controls, followed by replication in an additional 1088 cases and 845 controls.

RESULTS

The meta-analysis of Korean GWAS identified one novel locus for ulcerative colitis at rs76227733 on 10q24 [pcombined = 6.56 × 10-9] and two novel loci for Crohn's disease [CD] at rs2240751 on 19p13 [pcombined = 3.03 × 10-8] and rs6936629 on 6q22 [pcombined = 3.63 × 10-8]. Pathway-based analysis of GWAS data using MAGMA showed that the MHC and antigenic stimulus-related pathways were more significant in Korean CD, whereas cytokine and transcription factor-related pathways were more significant in European CD. Phenotype variance explained by the polygenic risk scores derived from Korean data explained up to 14% of the variance of CD whereas those derived from European data explained 10%, emphasizing the need for large-scale genetic studies in this population.

CONCLUSIONS

The identification of novel loci not previously associated with IBD suggests the importance of studying IBD genetics in diverse populations.

摘要

背景和目的

在多个人群中进行的炎症性肠病（IBD）全基因组关联研究（GWAS）已经确定了超过 240 个易感位点。我们之前进行了迄今为止最大规模的亚洲特异性 IBD GWAS，以确定两个新的 IBD 风险位点，并确认与 28 个已建立的位点相关。为了在亚洲人群中发现更多的易感位点，我们扩展了之前的研究设计，将病例数量增加一倍，使用新的 GWAS 数据集包括 1726 例病例和 378 例对照。

方法

对之前和新的 GWAS 数据集进行逆方差固定效应荟萃分析，共包括 3195 例病例和 4419 例对照，然后在另外 1088 例病例和 845 例对照中进行复制。

结果

韩国 GWAS 的荟萃分析确定了一个新的溃疡性结肠炎易感位点 rs76227733 位于 10q24 [pcombined = 6.56 × 10-9]，两个新的克罗恩病 [CD] 易感位点 rs2240751 位于 19p13 [pcombined = 3.03 × 10-8]和 rs6936629 位于 6q22 [pcombined = 3.63 × 10-8]。使用 MAGMA 对 GWAS 数据进行基于途径的分析表明，在韩国 CD 中，MHC 和抗原刺激相关途径更为显著，而在欧洲 CD 中，细胞因子和转录因子相关途径更为显著。来自韩国数据的多基因风险评分解释的表型方差高达 14%，而来自欧洲数据的解释为 10%，这强调了在该人群中进行大规模遗传研究的必要性。