METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes.
RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer.
CONCLUSIONS: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.
方法:从MSigDB数据库中提取免疫基因。将GI癌的全基因组关联研究(GWAS)摘要数据与与基因相关的表达定量性状基因座(eQTL)和DNA甲基化定量性状基因座(mQTL)进行整合。基于汇总数据的孟德尔随机化(SMR)和共定位分析用于揭示基因与胃肠道癌症之间的因果关系。敏感性分析采用双样本MR分析。单细胞分析阐明了基因的富集。
结果:三步SMR分析表明,一种假定的机制,cg17294865CpG位点调控HLA-DRA表达与胃癌风险呈负相关。HLA-DRA在胃癌中的单核细胞/巨噬细胞和骨髓细胞中的表达显着差异。
结论:这项研究提供了证据,表明上调HLA-DRA的表达水平可以降低胃癌的风险。