Integrative analysis identified mediation effects of lncRNAs on the correlations between methylation and mRNA.

The aim of this study was to construct DNA methylation-lncRNA-mRNA interaction trios in peripheral blood mononuclear cells. We first conducted eQTL analyses using genome-wide methylation, lncRNA and mRNA expression data from 43 Chinese females. Next, causal inference test (CIT) was used to detect the lncRNA mediation effects on methylation and mRNA. Methylation-lncRNA cis-eQTL analysis identified 11 significant cis-methylation-lncRNA pairs. Combined with the results from the next lncRNA-mRNA eQTL and methylation-mRNA eQTL analyses, the 11 significant pairs and their corresponding 11,204 target e-mRNAs formed 12,245 trios. Further CIT identified six lncRNAs as mediators in regulating the corresponding pairs between methylation and mRNA. This study detected lncRNAs with mediation effects on the correlations between DNA methylations and a large number of mRNAs.