Integrative Analysis Identifies Genetic Variants Associated With Autoimmune Diseases Affecting Putative MicroRNA Binding Sites
Abstract
Genome-wide and fine mapping studies have shown that more than 90% of genetic variants associated with autoimmune diseases (AID) are located in non-coding regions of the human genome and especially in regulatory sequences, including microRNAs (miRNA) target sites. MiRNAs are small endogenous noncoding RNAs that modulate gene expression at the post-transcriptional level. Single nucleotide polymorphisms (SNPs) located within the 3' untranslated region of their target mRNAs (miRSNP) can alter miRNA binding sites. Yet, little is known about their effect on regulation by miRNA and the consequences for AID. Conversely, it is well known that two or more AID may share part of their genetic background. Here, we hypothesized that miRSNPs could be associated with more than one AID. To identify miRSNPs associated with AID, we integrated results from three different prediction tools (Polymirts, miRSNP, and miRSNPscore) using a naïve Bayes classifier approach to identify miRSNPs predicted to affect binding sites of miRNAs. Further, to detect miRSNPs associated with two or more AID, we integrated predictions with summary statistics from 12 AID studies. In addition, to prioritize miRSNPs, miRNAs and AID-associated target genes, we used public ...Continue Reading
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Autoimmune Diseases
Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.