Integration of genome wide association study with gene expression profiling identifies ROR1 as a novel susceptibility gene for coronary artery disease

Objective To identify new susceptibility genes for coronary artery disease(CAD)by integrating genome wide association study and gene expression profiling. Methods On account of our data of genome wide association study(GWAS)on CAD, our integrative analysis of gene expression profiles and GWAS for CAD was conducted, and we obtained candidate genes and single nucleotide polymorphisms(SNPs)for a multicenter case-control genetic association study.Using a DNA ligase chain reaction-based genotyping method, we validated these candidate loci in two independent populations. Results Firstly, we selected 21 SNPs for 21 candidate genes.Using a DNA ligase chain reaction-based genotyping method, we validated these candidate loci in two independent populations, including population 1(495 cases and 492 control)and population 2(810 cases and 853 control). And we identified an intragenic SNP rs11208367(ROR1), which was significantly associated with CAD.Meta confluence analysis in combination of GWAS and two validation populations showed that the P value of rs11208367 was 2.00×10-4, which was still significant after Bonferroni multiple test correction(0.05/21=2.38×10-3). Conclusions The rs11208367 SNP of ROR1gene is significantly associated with CAD, indicating that ROR1is a novel susceptibility gene for CAD. Key words: Genomics; Coronary disease; Genetic predisposition to disease