Abstract
Micro RNA (miRNA) and its regulatory effect on messenger RNA (mRNA) gene expression are a major focus in cancer research. Disruption in the normal miRNA‐mRNA regulation network can result in serious cascading biological repercussions. In this study, we curated miRNA‐related variants from major genomic consortiums and thoroughly evaluated how these variants could exert their effects by cross‐validating with independent functional knowledge bases. Nearly all known variants (more than 664 million) categorized by type (germline, somatic, epigenetic) were mapped to the genomic regions involved in miRNA‐mRNA binding (miRNA seeds and miRNA‐mRNA 3’‐UTR binding sequence). Subsets of miRNA‐related variants supported by additional functional evidence, such as expression Quantitative Trait Loci (eQTL) and Genome‐Wide Association Study (GWAS), were identified and scrutinized. Our results show that variants in miRNA seeds can substantially alter the composition of a miRNA's target mRNA set. Various functional analyses converged to reveal a post‐transcriptional complex regulatory network where miRNA, eQTL, and RNA‐binding protein intertwined to disseminate the impact of genomic variants. These results may potentially explain how certain variants affect disease/trait risks in genome wide association studies.