Publication: Association study of coronary artery disease-associated genome-wide significant SNPS with coronary stenosis in Pakistani population
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Date
2020-01-23
Authors
Authors
Cheema, Asma Naseer
Pirim, Dilek
Wang, Xingbin
Ali, Jabar
Bhatti, Attya
John, Peter
Feingold, Eleanor
Demirci, F. Yeşim
Kamboh, M. Ilyas
Journal Title
Journal ISSN
Volume Title
Publisher
Hindawi
Abstract
Genome-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.
Description
Keywords
Risk, Identification, Inflammation, Genetics, Loci, Annotation, Discovery, Sortilin, Sort1, Biotechnology & applied microbiology, Genetics & heredity, Research & experimental medicine, Pathology