Abstract
To examine the potential causal genes for gastric cancer (GC) susceptibility and effective disease prognosis biomarkers. In this research, public single-cell RNA sequencing (scRNA-seq) data were applied to analyze different cell types and to identify differentially expressed genes (DEGs). The summary data-based Mendelian randomization (SMR) was employed to integrate genome-wide association studies (GWAS) with expression quantitative trait loci (eQTL) to investigate potential genes that causally associated with GC. Besides, a systematic SMR analysis with methylation quantitative trait loci (mQTL) was conducted to reveal the methylation regulatory relationship of GC-related pathogenic genes. In addition, bioinformatic tools including GeneMANIA, gene set enrichment analysis (GSEA), KM-plotter and immune infiltration analysis were used to further explore the biological mechanisms and functions of the candidate genes in GC. Seven cell types and 1707 cell type-specific DEGs were identified by scRNA-seq analysis. Using the SMR and HEIDI test, we screened out 9 genes by integrating GWAS with eQTL analysis from gastric tissue and 26 genes from whole blood. Based on the DEGs identified by scRNA-seq and SMR analysis, 4 positively related genes(HLA-DQB1、PSMB9、RPS18 and TAF1C)were prioritized as candidate GC-causal genes.KM-plotter indicated that aberrant expression of the candidate genes was significantly associated with the prognosis of GC patients. Immune infiltration analysis provides a theoretical basis for these candidate genes to become potential immunotherapeutic targets. These findings may give novel insight into the molecular mechanisms of GC and provide potential biomarkers for therapeutic interventions of GC.