Genome-wide pathway analysis in glioma

Abstract

The aim of this study was to identify candidate single-nucleotide polymorphisms (SNPs) that may play a role in the susceptibility to glioma, to elucidate their potential mechanisms, and to generate SNP-to-gene-to-pathway hypotheses. A genome-wide association study (GWAS) dataset of glioma including 509,345 SNPs from 1,856 glioma patients and 4,955 control subjects of European descent was used in this study. Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 6 candidate SNPs, 5 genes, and 9 pathways, which revealed 5 hypothetical biological mechanisms. The hypothetical mechanisms, beginning with the strongest, are summarized as follows: (i) rs667128 alters the role of taste receptor, type 2, member 8 (TAS2R8) in taste receptor activity and taste transduction pathways (p < 0.001, false discovery rate (FDR) < 0.001; p = 0.001, FDR = 0.012, respectively), (ii) rs619381 modulates the effect of taste receptor, type 2, member 7 (TAS2R7) on taste receptor activity and taste transduction (p < 0.001, FDR < 0.001; p = 0.001, FDR = 0.012), (iii) rs1033583 modulates delta-like protein 1 (DLL1), regulating cell adhesion and segment specification (p <0.001, FDR = 0.011; p = 0.001, FDR = 0.032), (iv) rs2232580 affects the role of lipopolysaccharide binding protein (LBP) in the response to lipopolysaccharide, positive regulation of interleukin-6 production, acute inflammatory response, and in macrophage activation (0.002 <= p <= 0.013; 0.012 <= FDR <= 0.030), and (v) rs4644 and rs4652 regulate lectin, galactoside-binding, soluble, 3 (LGALS3), affecting immunoglobulin binding (p = 0.010; FDR = 0.040). Using the ICSNPathway to analyze glioma GWAS data, 6 candidate SNPs, 5 genes (TAS2R8, TAS2R7, DLL1, LBP, and LGALS3), and 9 pathways that may contribute to the susceptibility of glioma were identified.