Integrating transcriptome-wide association study and copy number variation study identifies candidate genes and...

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.

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.

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).

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