{Reference Type}: Journal Article
{Title}: Integrating transcriptome-wide association study and copy number variation study identifies candidate genes and pathways for diffuse non-Hodgkin's lymphoma.
{Author}: Wu D;Zhao J;Ma H;Wang MC;
{Journal}: Cancer Genet
{Volume}: 243
{Issue}: 0
{Year}: 05 2020
暂无{DOI}: 10.1016/j.cancergen.2020.02.005
{Abstract}: 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.<BR>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.<BR>We identified 214 genes with TWAS P value < 0.05 for DNHL, such as MRPL19 (PTWAS = 0.0010), CRCP (PTWAS = 0.0010) and SEMA3C (PTWAS = 0.0010). After further comparing the 214 genes with copy number variations of DNHL patients, we found 1 overlapped gene, BCL10 (PTWAS = 0.0100). We also detected 6 common GO terms shared between gene set enrichment analysis results of TWAS and CNAs, such as cytosol (PTWAS = 0.0003, PCNAs = 4.99 × 10-7) and membrane (PTWAS = 0.0048, PCNAs = 0.0046). The pathway enrichment analysis of TWAS and CNAs detected 3 common pathways, including HIF-1 signaling pathway (PTWAS = 0.0195, PCNAs = 1.96 × 10-5), mTOR signaling pathway (PTWAS = 0.0242, PCNAs = 6.75 × 10-5) and adipocytokine signaling pathway (PTWAS = 0.0392, PCNAs = 0.0103).<BR>Our study identified multiple DNHL associated genes and pathways, providing novel useful information for the pathogenetic studies of DNHL.