转录组学结合全基因组关联分析鉴定ROR1为冠心病新易感基因

摘要

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 (ROR 1),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.%目的 本研究将结合转录组学和全基因组关联分析,鉴定新的冠状动脉心脏病(冠心病)易感基因. 方法 利用冠心病全基因组关联研究(genome-wide association study,GWAS)数据,结合动脉粥样硬化相关转录组学分析,初步筛选得到候选基因和位点,然后进行多中心病例-对照遗传关联分析.通过等位基因特异性DNA连接酶链式反应,在两个独立人群中进行候选位点的分型,验证其与冠心病的相关性. 结果 初步筛选得到21个候选基因上的21个候选位点;经过包括2650例汉族冠心病病例和对照的两个独立人群验证后,ROR1基因的rs11208367位点显示与冠心病显著的相关性.Meta整合分析发现rs11208367位点的P值为2.00×10-4,达到Bonferroni多重检验P值阈值(0.05/21=2.38×10-3). 结论 ROR1基因上的rs11208367位点与冠心病相关,ROR1基因可能是新的冠心病易感基因.