Genome-wide identification of microRNA expression quantitative trait loci

Nat Commun. 2015 Mar 20;6:6601. doi: 10.1038/ncomms7601.

Abstract

Identification of microRNA expression quantitative trait loci (miR-eQTL) can yield insights into regulatory mechanisms of microRNA transcription, and can help elucidate the role of microRNA as mediators of complex traits. Here we present a miR-eQTL mapping study of whole blood from 5,239 individuals, and identify 5,269 cis-miR-eQTLs for 76 mature microRNAs. Forty-nine per cent of cis-miR-eQTLs are located 300-500 kb upstream of their associated intergenic microRNAs, suggesting that distal regulatory elements may affect the interindividual variability in microRNA expression levels. We find that cis-miR-eQTLs are highly enriched for cis-mRNA-eQTLs and regulatory single nucleotide polymorphisms. Among 243 cis-miR-eQTLs that were reported to be associated with complex traits in prior genome-wide association studies, many cis-miR-eQTLs miRNAs display differential expression in relation to the corresponding trait (for example, rs7115089, miR-125b-5p and high-density lipoprotein cholesterol). Our study provides a roadmap for understanding the genetic basis of miRNA expression, and sheds light on miRNA involvement in a variety of complex traits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Chromosome Mapping
  • Female
  • Gene Expression Profiling
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci / genetics*
  • Regulatory Sequences, Nucleic Acid
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • MicroRNAs

Associated data

  • dbGaP/PHS000007