整合全转录组关联研究和拷贝数变异研究可鉴定弥漫性非霍奇金淋巴瘤的候选基因和通路。

Integrating transcriptome-wide association study and copy number variation study identifies candidate genes and pathways for diffuse non-Hodgkin's lymphoma.

作者信息

Wu Di, Zhao Jing, Ma Hong, Wang Meng-Chang

机构信息

Department of hematology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, China.

出版信息

Cancer Genet. 2020 May;243:7-10. doi: 10.1016/j.cancergen.2020.02.005. Epub 2020 Feb 25.

DOI:10.1016/j.cancergen.2020.02.005

PMID:32179489

Abstract

BACKGROUND

The genetic basis of diffuse non-Hodgkin's lymphoma (DNHL) is largely unknown now. We conducted a large-scale transcriptome-wide association study (TWAS) of DNHL to identify novel candidates for DNHL.

METHODS

The GWAS summary data of DNHL was obtained from the UKBiobank, involving 685 cases and 451,579 controls. TWAS of DNHL was performed using tissue-specific gene expression weights generated from the Genotype-Tissue Expression (GTEx) data. The DNHLTWAS results were further validated by a previous published copy number alterations (CNA) study of DNHL. Gene ontology (GO) and pathway enrichment analysis of identified candidate genes were conducted by the DAVID 6.8.

RESULTS

We identified 214 genes with TWAS P value < 0.05 for DNHL, such as MRPL19 (P = 0.0010), CRCP (P = 0.0010) and SEMA3C (P = 0.0010). After further comparing the 214 genes with copy number variations of DNHL patients, we found 1 overlapped gene, BCL10 (P = 0.0100). We also detected 6 common GO terms shared between gene set enrichment analysis results of TWAS and CNAs, such as cytosol (P = 0.0003, PCNAs = 4.99 × 10) and membrane (P = 0.0048, P = 0.0046). The pathway enrichment analysis of TWAS and CNAs detected 3 common pathways, including HIF-1 signaling pathway (P = 0.0195, P = 1.96 × 10), mTOR signaling pathway (P = 0.0242, P = 6.75 × 10) and adipocytokine signaling pathway (P = 0.0392, P = 0.0103).

CONCLUSIONS

Our study identified multiple DNHL associated genes and pathways, providing novel useful information for the pathogenetic studies of DNHL.

摘要

背景

弥漫性非霍奇金淋巴瘤（DNHL）的遗传基础目前很大程度上尚不明确。我们开展了一项大规模的DNHL全转录组关联研究（TWAS），以识别DNHL的新候选基因。

方法

DNHL的全基因组关联研究（GWAS）汇总数据来自英国生物银行，包括685例病例和451,579例对照。使用从基因型-组织表达（GTEx）数据生成的组织特异性基因表达权重进行DNHL的TWAS。DNHL的TWAS结果通过先前发表的DNHL拷贝数改变（CNA）研究进一步验证。通过DAVID 6.8对鉴定出的候选基因进行基因本体（GO）和通路富集分析。

结果

我们鉴定出214个基因，其DNHL的TWAS P值<0.05，如MRPL19（P = 0.0010）、CRCP（P = 0.0010）和SEMA3C（P = 0.0010）。在将这214个基因与DNHL患者的拷贝数变异进一步比较后，我们发现1个重叠基因，即BCL10（P = 0.0100）。我们还在TWAS和CNA的基因集富集分析结果之间检测到6个共同的GO术语，如胞质溶胶（P = 0.0003，PCNAs = 4.99×10）和膜（P = 0.0048，P = 0.0046）。TWAS和CNA的通路富集分析检测到3条共同通路，包括HIF-1信号通路（P = 0.0195，P = 1.96×10）、mTOR信号通路（P = 0.0242，P = 6.75×10）和脂肪细胞因子信号通路（P = 0.0392，P = 0.0103）。