memo-eQTL: DNA methylation modulated genetic variant effect on gene transcriptional regulation

Abstract

Expression quantitative trait locus (eQTL) analysis has become an important tool in understanding the link between genetic variants and gene expression, ultimately helping to bridge the gap between risk SNPs and associated diseases. Recently, we identified and validated a specific case where the methylation of a CpG site can affect the relationship between the genetic variant and gene expression. To systematically evaluate this regulatory mechanism, we developed an extended eQTL mapping method named DNA methylation modulated eQTL (memo-eQTL). We performed memo-eQTL mapping in 128 normal prostate samples and discovered 1,731 memo-eQTLs, a vast majority of which have not been reported as eQTLs. We found that the methylation of the memo-eQTL CpG sites can either enhance or insulate the interaction between SNP and Gene expression by altering CTCF-based chromatin 3D structure. This study demonstrated the prevalence of memo-eQTLs, which can enable the identification of novel causal genes for traits or diseases associated with genetic variations.