Anti-PSRC1 (full length) polyclonal antibody

Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Here we describe an approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs. We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. We observed a clear association between rs12740374 and lipid accumulation and gene expression in differentiated hepatocytes, in particular, expression of SORT1, CELSR2, and PSRC1, consistent with previous analyses of this variant using other approaches. Initial investigation of additional SNPs also highlighted correlations with gene expression. These findings suggest that iPSC-based population studies hold promise as tools for the functional validation of GWAS variants.

Recent genome-wide association studies (GWAS) have identified genetic variants associated with coronary artery disease (CAD), ischemic stroke (IS) and serum lipid traits in different ethnic groups. Some loci were found to affect the risk of CAD and IS. However, there were no data in the southern Chinese populations. Our study was to assess the association of CELSR2-PSRC1-SORT1 rs599839, rs464218 and rs6698443 SNPs and serum lipid levels and the risk of CAD and IS. The genotypes of 3 SNPs were detected in 561 CAD and 527 IS patients, and in 590 healthy controls. The genotypic and allelic frequencies of the rs599839 SNP were different between the controls and IS patients (P < 0.05). The minor G alleles of rs599839 and rs464218 SNPs were associated with higher high-density lipoprotein cholesterol concentrations in CAD and IS patients (P < 0.05); respectively. No association was found between the SNPs of rs599839, rs464218 and rs6698843 at the CELSR2-PSRC1-SORT1 and the risk of CAD or IS. These results will be replicated in the other Chinese populations.