PLoS genetics
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Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with trait diversity and disease susceptibility, yet their functional properties often remain unclear. It has been hypothesized that SNPs in microRNA binding sites may disrupt gene regulation by microRNAs (miRNAs), short non-coding RNAs that bind to mRNA and downregulate the target gene. While several studies have predicted the location of SNPs in miRNA binding sites, to date there has been no comprehensive analysis of their impact on miRNA regulation. ⋯ We draw on these results as a starting point to assess whether SNPs on dysregulated pathways are responsible for miRNA dysregulation of individual genes in tumors. Using an integrative regression analysis that incorporates miRNA expression, mRNA expression, and SNP genotype data, we identify functional SNPs that we term "regulatory QTLs (regQTLs)": loci whose alleles impact the regulation of genes by miRNAs. We apply the method to breast, liver, lung, and prostate cancer data from The Cancer Genome Atlas, and provide a tool to explore the findings.