GWAS in two Saudi Myocardial Infarction Cohorts and European based studies reveal dozens of concordant signals

Abstract

Abstract Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of MI although studies in non-European are still lacking. Saudi Arabian cohorts offers the opportunity for discovery of novel genetic variants impacting disease risk due to the high rate of consanguinity. GWG imputation and GWAS followed by meta-analysis was performed on two independent Saudi Arabian studies comprising 3,950 MI cases and 2,324 non-MI controls. Meta-analyses were then performed with the two Saudi MI studies and the CardioGRAMplusC4D and the UK BioBank GWAS as controls Meta-analyses of the two Saudi MI studies resulted in 17 SNPs reaching genome-wide significance. Meta-analyses of all 4 studies revealed 66 loci reaching genome-wide significance levels of p < 5 x 10− 8. All of these variants with the exception of rs2764203 have previously been reported as MI associated loci or are in high linkage disequilibrium with known loci. One SNP association in Shisa family member 5 (SHISA5) (rs11707229), is evident at a much higher frequency in Saudi MI populations (> 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi only GWAS (meta-analyses) several new loci were implicated that would require future studies for validation and functional analyses.