BACKGROUND Coronary artery disease (CAD) and plasma lipid levels are highly correlated, indicating the presence of common pathways between them. Nevertheless, the molecular pathways underlying the pathogenic comorbidities for both traits remain poorly studied. We sought to identify common pathways and key driver genes by performing a comprehensive integrative analysis based on multi-omic datasets. METHODS By performing a pathway-based analysis of GWAS summary data, we identified that lipoprotein metabolism process-related pathways were significantly associated with CAD risk. Based on LD score regression analysis of CAD-related SNPs, significant heritability enrichments were observed in the cardiovascular and digestive system, as well as in liver and gastrointestinal tissues, which are the main regulators for lipid level. RESULTS We found there existed significant genetic correlation between CAD and other lipid metabolism related traits (the smallest P value < 1 × 10- 16). A total of 13 genes (e.g., LPA, APOC1, APOE and SLC22A3) was found to be overlapped between CAD and plasma lipid levels. By using the data-driven approach that integrated transcriptome information, we discovered co-expression modules associated prominently with both CAD and plasma lipids. With the detailed topology information on gene-gene regulatory relationship, we illustrated that the identified hub genes played important roles in the pathogenesis of CAD and plasma lipid turbulence. CONCLUSION Together, we identified the shared molecular mechanisms underlying the correlation between CAD and plasma lipid levels.

中文翻译：

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综合基因组分析确定了冠状动脉疾病与血脂水平之间相关性的常见调控网络。

背景技术冠状动脉疾病（CAD）和血浆脂质水平高度相关，表明它们之间存在共同的途径。然而，这两种性状的致病合并症的分子途径仍未得到很好的研究。我们力求通过基于多组学数据集进行全面的综合分析，以鉴定常见途径和关键驱动基因。方法通过对GWAS汇总数据进行基于路径的分析，我们发现脂蛋白代谢过程相关的路径与CAD风险显着相关。根据与CAD相关的SNP的LD评分回归分析，在心血管和消化系统以及肝脏和胃肠组织（这是脂质水平的主要调节剂）中观察到了显着的遗传力富集。结果我们发现CAD与其他脂质代谢相关性状之间存在显着的遗传相关性（最小P值<1×10-16）。发现总共13个基因（例如LPA，APOC1，APOE和SLC22A3）在CAD和血浆脂质水平之间重叠。通过使用整合转录组信息的数据驱动方法，我们发现了与CAD和血浆脂质显着相关的共表达模块。借助有关基因与基因调节关系的详细拓扑信息，我们说明了已鉴定的中枢基因在CAD和血浆脂质湍流的发病机理中起着重要作用。结论我们一起确定了CAD和血浆脂质水平之间相关性的共同分子机制。