Integrative Analysis Identifies Genetic Variants Associated With Autoimmune Diseases Affecting Putative MicroRNA Binding Sites

Frontiers in Genetics
Rodrigo C de AlmeidaMaria L Petzl-Erler

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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Citations

Jul 6, 2019·Frontiers in Endocrinology·Krisztina BanfaiKrisztian Kvell
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Dec 7, 2021·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Xinzhen ChenJing Wu

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Methods Mentioned

BETA
chip
chips
RNA-seq
genotyping
CLIP-seq
ubiquitination

Software Mentioned

Immunochip
LDlink
PolymiRTS
BloodeQTLBrowser
GTEx
Blood eQTL Browser
miRanda
R R Development Core Team
TargetScan
MirSNPscore

Related Concepts

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