Jung Seulgi, Liu Wenting, Baek Jiwon, Moon Jung Won, Ye Byong Duk, Lee Ho-Su, Park Sang Hyoung, Yang Suk-Kyun, Han Buhm, Liu Jianjun, Song Kyuyoung
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, South Korea.
Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
Front Genet. 2020 May 14;11:486. doi: 10.3389/fgene.2020.00486. eCollection 2020.
Expression quantitative trait loci (eQTL) datasets have extensively been used to help interpret genome-wide association study signals. Most eQTL analyses have been conducted with populations of European ancestry.
To determine the most functionally relevant genes at the Crohn's disease (CD) loci identified in genome-wide association studies (GWAS) involving Asian populations and to find novel disease-associated genes, we conducted an eQTL analysis.
eQTL analysis was performed using whole-blood RNA-sequencing of 101 Korean patients with CD. FastQTL was used for a pair-wise genome analysis of ∼ 6.5 M SNPs and ∼ 22 K transcripts.
We identified 135,164 eQTL and 3,816 eGenes with a false discovery rate less than 0.05. A significant proportion of the genes identified in our study overlapped with those identified in previous studies. The significantly enriched pathways of these 3,816 eGenes included neutrophil degranulation and small molecule biosynthetic process. Integrated analysis of CD GWAS with Korean eQTL revealed two putative target genes, and , at two previously reported loci, whereas only with the whole blood data from the Genotype-Tissue Expression (GTEx) project, highlighting the utility of building a population-specific data set, even of modest size. The risk alleles of these genes were found to be associated with lower expression levels of and , respectively. Our eQTL browser can be accessed at "http://asan.crohneqtl.com/".
This resource would be useful for studies that need to employ genome-wide association analyses involving Asian populations.
表达定量性状基因座（eQTL）数据集已被广泛用于帮助解释全基因组关联研究信号。大多数eQTL分析是在欧洲血统人群中进行的。
为了确定在涉及亚洲人群的全基因组关联研究（GWAS）中确定的克罗恩病（CD）基因座上最具功能相关性的基因，并寻找新的疾病相关基因，我们进行了一项eQTL分析。
使用101名韩国CD患者的全血RNA测序进行eQTL分析。FastQTL用于对约650万个单核苷酸多态性（SNP）和约2.2万个转录本进行成对基因组分析。
我们鉴定出135164个eQTL和3816个e基因，错误发现率小于0.05。我们研究中鉴定出的基因中有很大一部分与先前研究中鉴定出的基因重叠。这3816个e基因显著富集的通路包括中性粒细胞脱颗粒和小分子生物合成过程。对韩国eQTL的CD GWAS进行综合分析，在两个先前报道的基因座上揭示了两个假定的靶基因，而只有与基因型-组织表达（GTEx）项目的全血数据重叠，这突出了构建特定人群数据集的实用性，即使规模不大。发现这些基因的风险等位基因分别与 和 的较低表达水平相关。我们的eQTL浏览器可在“http://asan.crohneqtl.com/”访问。
该资源将有助于需要对亚洲人群进行全基因组关联分析的研究。
