Association study of coronary artery disease-associated genome-wide significant SNPS with coronary stenosis in Pakistani population

Cheema, Asma NaseerPirim, DilekWang, XingbinAli, JabarBhatti, AttyaJohn, PeterFeingold, EleanorDemirci, F. YeşimKamboh, M. Ilyas2024-07-092024-07-092020-01-230278-0240https://doi.org/10.1155/2020/9738567https://onlinelibrary.wiley.com/doi/10.1155/2020/9738567https://hdl.handle.net/11452/43098Genome-wide association studies (GWAS) of coronary artery disease (CAD) have revealed multiple genetic risk loci. We assessed the association of 47 genome-wide significant single-nucleotide polymorphisms (SNPs) at 43 CAD loci with coronary stenosis in a Pakistani sample comprising 663 clinically ascertained and angiographically confirmed cases. Genotypes were determined using the iPLEX Gold technology. All statistical analyses were performed using R software. Linkage disequilibrium (LD) between significant SNPs was determined using SNAP web portal, and functional annotation of SNPs was performed using the RegulomeDB and Genotype-Tissue Expression (GTEx) databases. Genotyping comparison was made between cases with severe stenosis (>= 70%) and mild/minimal stenosis (<30%). Five SNPs demonstrated significant associations: three with additive genetic modelsPLG/rs4252120 (p=0.0078),KIAA1462/rs2505083 (p=0.005), andSLC22A3/rs2048327 (p=0.045) and two with recessive modelsSORT1/rs602633 (p=0.005) andUBE2Z/rs46522 (p=0.03).PLG/rs4252120 was in LD with two functionalPLGvariants (rs4252126 and rs4252135), each with a RegulomeDB score of 1f. Likewise,KIAA1462/rs2505083 was in LD with a functional SNP,KIAA1462/rs3739998, having a RegulomeDB score of 2b. In the GTEx database,KIAA1462/rs2505083,SLC22A3/rs2048327,SORT1/rs602633, andUBE2Z/rs46522 SNPs were found to be expression quantitative trait loci (eQTLs) in CAD-associated tissues. In conclusion, five genome-wide significant SNPs previously reported in European GWAS were replicated in the Pakistani sample. Further association studies on larger non-European populations are needed to understand the worldwide genetic architecture of CAD.eninfo:eu-repo/semantics/openAccessRiskIdentificationInflammationGeneticsLociAnnotationDiscoverySortilinSort1Biotechnology & applied microbiologyGenetics & heredityResearch & experimental medicinePathologyAssociation study of coronary artery disease-associated genome-wide significant SNPS with coronary stenosis in Pakistani populationArticle000549971800002202010.1155/2020/9738567