Identification of Single Nucleotide Polymorphisms Regulating Peripheral Blood mRNA Expression with Genome-Wide Significance: An eQTL Study in the Japanese Population

Several recent studies have reported that expression quantitative trait loci (eQTLs) may affect gene expression in a cell-dependent manner. In the current study, a genome-wide eQTL analysis was performed in whole blood samples collected from 76 Japanese subjects. RNA microarray analysis was performed for 3 independent sample groups that were genotyped in a genome-wide scan. The correlations between the genotypes of 534,404 autosomal single nucleotide polymorphisms (SNPs) and the expression levels of 30,465 probes were examined for each sample group. The SNP-probe pairs with combined correlation coefficients of all 3 sample groups corresponding to P<3.1×10(−12) (i.e., Bonferroni-corrected P<0.05) were considered significant. SNP-probe pairs with a high likelihood of cross-hybridization and SNP-in-probe effects were excluded to avoid false positive results. We identified 102 cis-acting and 5 trans-acting eQTL regions. The cis-eQTL regions were widely distributed both upstream and downstream of the gene, as well as within the gene. The eQTL SNPs identified were examined for their influence on the expression levels in lymphoblastoid cell lines by using a public database. The results showed that genetic variants affecting expression levels in whole blood may have different effects on gene expression in lymphoblastoid cell lines. Further studies are required to clarify how SNPs function in affecting the expression levels in whole blood as well as in other tissues.