Abstract
BackgroundCoronary 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.MethodsBy 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.ResultsWe 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.ConclusionTogether, we identified the shared molecular mechanisms underlying the correlation between CAD and plasma lipid levels.
Highlights
Coronary artery disease (CAD) and plasma lipid levels are highly correlated, indicating the presence of common pathways between them
CAD associated pathways are enriched in lipoprotein metabolism processes To reveal the genetic architecture of CAD, we first performed pathway analysis to test the associations of predefined functional gene-sets, including Kyoto encyclopedia of genes and genomes (KEGG), GO, BioCarta, and Reactome. 4608 pathways with a size 5–300 genes per pathway were retained for downstream analyses in consideration of appropriate specificity and high efficiency
These pathways contained 10 common genes, i.e., LDLR, LPA, PLG, APOE, LIPA, LPL, APOB, ABCG8, ABCG5, APOC4 (Additional file 2: Table S4), that were significantly associated with CAD (P < 2.72 × 10− 06) by using the marker Analysis of GenoMic Annotation (MAGMA) analysis
Summary
Coronary artery disease (CAD) and plasma lipid levels are highly correlated, indicating the presence of common pathways between them. We sought to identify common pathways and key driver genes by performing a comprehensive integrative analysis based on multi-omic datasets. Genomewide association studies (GWAS) have successfully identified more than hundreds of risk loci for CAD and plasma lipid levels [3,4,5,6]. Several genetic studies suggest the existence of shared polygenic pleiotropy between CAD and blood lipids [4, 7, 8]. The genes APOA5, TRIB1 and APOC3, which were significantly associated with plasma lipids, showed prominent risk to CAD [9, 10]. Due to lack of multi-dimensional data integration analysis, the
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
