title: Inferring causative variants in microRNA target sites.
abstract: 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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway. laurent.thomas@ntnu.no
authors.forename: Laurent F
authors.initials: LF
authors.lastname: Thomas
authors.forename: Takaya
authors.initials: T
authors.lastname: Saito
authors.forename: Pål
authors.initials: P
authors.lastname: Sætrom
mesh_terms: D000483:Alleles; D001249:Asthma / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D004194:Disease / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D035683:MicroRNAs