Integration of summary data from GWAS and eQTL studies identified novel risk genes for coronary artery disease
Yigang Zhong, Liuying Chen, Jinɡjinɡ Li, Yinghao Yao, Qiang Liu, Kaimeng Niu, Yunlong Ma, Yizhou Xu
Abstract
ABSTRACT: Several genetic loci have been reported to be significantly associated with coronary artery disease (CAD) by multiple genome-wide association studies (GWAS). Nevertheless, the biological and functional effects of these genetic variants on CAD remain largely equivocal. In the current study, we performed an integrative genomics analysis by integrating large-scale GWAS data (N = 459,534) and 2 independent expression quantitative trait loci (eQTL) datasets (N = 1890) to determine whether CAD-associated risk single nucleotide polymorphisms (SNPs) exert regulatory effects on gene expression. By using Sherlock Bayesian, MAGMA gene-based, multidimensional scaling (MDS), functional enrichment, and in silico permutation analyses for independent technical and biological replications, we highlighted 4 susceptible genes (CHCHD1, TUBG1, LY6G6C, and MRPS17) associated with CAD risk. Based on the protein-protein interaction (PPI) network analysis, these 4 genes were found to interact with each other. We detected a remarkably altered co-expression pattern among these 4 genes between CAD patients and controls. In addition, 3 genes of CHCHD1 (P = .0013), TUBG1 (P = .004), and LY6G6C (P = .038) showed significantly different expressions between CAD patients and controls. Together, we provide evidence to support that these identified genes such as CHCHD1 and TUBG1 are indicative factors of CAD.