Inferring causative variants in microRNA target sites

MicroRNAs (miRNAs) regulate genes post transcription by pairing with messenger RNA (mRNA). Variants such as single nucleotide polymorphisms (SNPs) in miRNA regulatory regions might result in altered protein levels and disease. Genome-wide association studies (GWAS) aim at identifying genomic regions...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2011-09, Vol.39 (16), p.e109-e109
Main Authors: Thomas, Laurent F, Saito, Takaya, Sætrom, Pål
Format: Article
Language:English
Subjects:
Alleles
Asthma - genetics
Breast Neoplasms - genetics
Computational Biology - methods
Disease - genetics
Female
Gene Expression Regulation
Genome-Wide Association Study
Humans
Methods Online
MicroRNAs - metabolism
Parkinson Disease - genetics
Polymorphism, Single Nucleotide
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:MicroRNAs (miRNAs) regulate genes post transcription by pairing with messenger RNA (mRNA). Variants such as single nucleotide polymorphisms (SNPs) in miRNA regulatory regions might result in altered protein levels and disease. Genome-wide association studies (GWAS) aim at identifying genomic regions that contain variants associated with disease, but lack tools for finding causative variants. We present a computational tool that can help identifying SNPs associated with diseases, by focusing on SNPs affecting miRNA-regulation of genes. The tool predicts the effects of SNPs in miRNA target sites and uses linkage disequilibrium to map these miRNA-related variants to SNPs of interest in GWAS. We compared our predicted SNP effects in miRNA target sites with measured SNP effects from allelic imbalance sequencing. Our predictions fit measured effects better than effects based on differences in free energy or differences of TargetScan context scores. We also used our tool to analyse data from published breast cancer and Parkinson's disease GWAS and significant trait-associated SNPs from the NHGRI GWAS Catalog. A database of predicted SNP effects is available at http://www.bigr.medisin.ntnu.no/mirsnpscore/. The database is based on haplotype data from the CEU HapMap population and miRNAs from miRBase 16.0.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkr414