Identification of cis- and trans-regulatory variation modulating microRNA expression levels in human fibroblasts (original) (raw)

  1. Samuel Deutsch1,
  2. Audrey Letourneau,
  3. Eugenia Migliavacca,
  4. Stephen B. Montgomery,
  5. Antigone S. Dimas2,
  6. Charles E. Vejnar,
  7. Homa Attar,
  8. Maryline Gagnebin,
  9. Corinne Gehrig,
  10. Emilie Falconnet,
  11. Yann Dupré,
  12. Emmanouil T. Dermitzakis and
  13. Stylianos E. Antonarakis3
  14. Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 1211, Switzerland
  1. ↵1 These authors contributed equally to this work.

Abstract

MicroRNAs (miRNAs) are regulatory noncoding RNAs that affect the production of a significant fraction of human mRNAs via post-transcriptional regulation. Interindividual variation of the miRNA expression levels is likely to influence the expression of miRNA target genes and may therefore contribute to phenotypic differences in humans, including susceptibility to common disorders. The extent to which miRNA levels are genetically controlled is largely unknown. In this report, we assayed the expression levels of miRNAs in primary fibroblasts from 180 European newborns of the GenCord project and performed association analysis to identify eQTLs (expression quantitative traits loci). We detected robust expression for 121 miRNAs out of 365 interrogated. We have identified significant _cis_- (10%) and _trans_- (11%) eQTLs. Furthermore, we detected one genomic locus (rs1522653) that influences the expression levels of five miRNAs, thus unraveling a novel mechanism for coregulation of miRNA expression.

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