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Cis-acting polymorphisms affect complex traits through modifications of microRNA regulation pathways.
PLoS ONE 7:e36694 (2012)
Genome-wide association studies (GWAS) have become an effective tool to map genes and regions contributing to multifactorial human diseases and traits. A comparably small number of variants identified by GWAS are known to have a direct effect on protein structure whereas the majority of variants is thought to exert their moderate influences on the phenotype through regulatory changes in mRNA expression. MicroRNAs (miRNAs) have been identified as powerful posttranscriptional regulators of mRNAs. Binding to their target sites, which are mostly located within the 3'-untranslated region (3'-UTR) of mRNA transcripts, they modulate mRNA expression and stability. Until today almost all human mRNA transcripts are known to harbor at least one miRNA target site with an average of over 20 miRNA target sites per transcript. Among 5,101 GWAS-identified sentinel single nucleotide polymorphisms (SNPs) that correspond to 18,884 SNPs in linkage disequilibrium (LD) with the sentinels (r(2) >= 0.8) we identified a significant overrepresentation of SNPs that affect the 3'-UTR of genes (OR = 2.33, 95% CI = 2.12-2.57, P
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
PRIMARY BILIARY-CIRRHOSIS; GENOME-WIDE ASSOCIATION; MESSENGER-RNA POLYADENYLATION; LARGE GENE LISTS; HUMAN-DISEASE; DNA-REPAIR; HEPATOCELLULAR-CARCINOMA; INTEGRATIVE ANALYSIS; UNFINISHED BUSINESS; EXPRESSION PROFILES
ISSN (print) / ISBN
1932-6203
Journal
PLoS ONE
Quellenangaben
Volume: 7,
Issue: 5,
Article Number: e36694
Publisher
Public Library of Science (PLoS)
Publishing Place
Lawrence, Kan.
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Reviewing status
Peer reviewed