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_TWAS = 0.0010), CRCP (P_TWAS = 0.0010) and SEMA3C (P_TWAS = 0.0010). After further comparing the 214 genes with copy number variations of DNHL patients, we found 1 overlapped gene, BCL10 (P_TWAS = 0.0100). We also detected 6 common GO terms shared between gene set enrichment analysis results of TWAS and CNAs, such as cytosol (P_TWAS = 0.0003, PCNAs = 4.99 × 10⁻⁷) and membrane (P_TWAS = 0.0048, P_CNAs = 0.0046). The pathway enrichment analysis of TWAS and CNAs detected 3 common pathways, including HIF-1 signaling pathway (P_TWAS = 0.0195, P_CNAs = 1.96 × 10⁻⁵), mTOR signaling pathway (P_TWAS = 0.0242, P_CNAs = 6.75 × 10⁻⁵) and adipocytokine signaling pathway (P_TWAS = 0.0392, P_CNAs = 0.0103).

Conclusions

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

中文翻译：

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整合转录组范围的关联研究和拷贝数变异研究确定了弥漫性非霍奇金淋巴瘤的候选基因和途径。

背景

弥漫性非霍奇金淋巴瘤（DNHL）的遗传基础现在是未知的。我们进行了DNHL的大规模转录组关联研究（TWAS），以确定DNHL的新候选者。

方法

DNHL的GWAS摘要数据从UKBiobank获得，涉及685例病例和451,579例对照。DNHL的TWAS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。DNHLTWAS结果已通过先前发布的DNHL拷贝数变更（CNA）研究得到了进一步验证。DAVID 6.8进行了基因本体（GO）和已鉴定候选基因的途径富集分析。

结果

我们鉴定了DNHL的TWAS P值<0.05的214个基因，例如MRPL19（P _TWAS  = 0.0010），CRCP（P _TWAS  = 0.0010）和SEMA3C（P _TWAS  = 0.0010）。在进一步比较214个基因与DNHL患者的拷贝数变异后，我们发现了1个重叠基因BCL10（P _TWAS  = 0.0100）。我们还检测了TWAS和CNA的基因集富集分析结果之间共有的6个通用GO术语，例如胞质溶胶（P _TWAS  = 0.0003，PCNAs = 4.99×10 ^-7）和膜（P _TWAS  = 0.0048，P_CNA  = 0.0046）。TWAS和CNA的途径富集分析检测到3条常见途径，包括HIF-1信号途径（P _TWAS  = 0.0195，P _CNAs  = 1.96×10 ^-5），mTOR信号途径（P _TWAS  = 0.0242，P _CNAs  = 6.75×10）^-5）和脂肪细胞因子信号通路（P _TWAS  = 0.0392，P _CNAs  = 0.0103）。

结论

我们的研究确定了多个与DNHL相关的基因和途径，为DNHL的致病性研究提供了新的有用信息。