MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs.

Chenxing Liu,Ming Lu,Weihua Yue,Lifang Wang,Tingting Li,Fuquan Zhang,Dai Zhang

doi:10.1186/1471-2164-13-661

Abstract

BackgroundNumerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3’UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3’UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers.DescriptionWe developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp), which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398), which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p < 0.0001) were found in the schizophrenia GWAS. Our findings identified the possible functions of these SNP loci, and provide the basis for subsequent functional research.ConclusionMirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.

Highlights

Numerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci studies
To help identifying putative miRNA-related Single nucleotide polymorphism (SNP) from researchers’ own GWAS and cis-acting Expression quantitative trait locus (eQTL) data set, we have developed a freely available database, named “MirSNP”, which provides SNPs located in predicted miRNA target sites
SNPs located in miRNA-mRNA binding sites could affect the expression of their host genes; we only considered eQTLs that had a cis-effect on the host genes

Summary

Introduction

Numerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies Few of these SNPs have explicit biological functions. MiRNAs are key regulators of gene expression; SNPs in the seed sites of miRNA targets may create, as well as destroy, miRNA binding sites, and further affect phenotypes and disease susceptibility [8]. Identifying these seedsite SNPs could help in the further exploration of the molecular mechanism of gene dysregulation. Certain polymorphisms in miRNA genes have been found to be associated with various complex diseases, including cancers, mental diseases, cardiomyopathy, and asthma (Additional file 1: Table S1)

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