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Comprehensive Exploration of the Effects of miRNA SNPs on Monocyte Gene Expression

Author

Listed:
  • Nicolas Greliche
  • Tanja Zeller
  • Philipp S Wild
  • Maxime Rotival
  • Arne Schillert
  • Andreas Ziegler
  • Panos Deloukas
  • Jeanette Erdmann
  • Christian Hengstenberg
  • Willem H Ouwehand
  • Nilesh J Samani
  • Heribert Schunkert
  • Thomas Munzel
  • Karl J Lackner
  • François Cambien
  • Alison H Goodall
  • Laurence Tiret
  • Stefan Blankenberg
  • David-Alexandre Trégouët
  • Cardiogenics Consortium

Abstract

We aimed to assess whether pri-miRNA SNPs (miSNPs) could influence monocyte gene expression, either through marginal association or by interacting with polymorphisms located in 3'UTR regions (3utrSNPs). We then conducted a genome-wide search for marginal miSNPs effects and pairwise miSNPs × 3utrSNPs interactions in a sample of 1,467 individuals for which genome-wide monocyte expression and genotype data were available. Statistical associations that survived multiple testing correction were tested for replication in an independent sample of 758 individuals with both monocyte gene expression and genotype data. In both studies, the hsa-mir-1279 rs1463335 was found to modulate in cis the expression of LYZ and in trans the expression of CNTN6, CTRC, COPZ2, KRT9, LRRFIP1, NOD1, PCDHA6, ST5 and TRAF3IP2 genes, supporting the role of hsa-mir-1279 as a regulator of several genes in monocytes. In addition, we identified two robust miSNPs × 3utrSNPs interactions, one involving HLA-DPB1 rs1042448 and hsa-mir-219-1 rs107822, the second the H1F0 rs1894644 and hsa-mir-659 rs5750504, modulating the expression of the associated genes. As some of the aforementioned genes have previously been reported to reside at disease-associated loci, our findings provide novel arguments supporting the hypothesis that the genetic variability of miRNAs could also contribute to the susceptibility to human diseases.

Suggested Citation

  • Nicolas Greliche & Tanja Zeller & Philipp S Wild & Maxime Rotival & Arne Schillert & Andreas Ziegler & Panos Deloukas & Jeanette Erdmann & Christian Hengstenberg & Willem H Ouwehand & Nilesh J Samani , 2012. "Comprehensive Exploration of the Effects of miRNA SNPs on Monocyte Gene Expression," PLOS ONE, Public Library of Science, vol. 7(9), pages 1-12, September.
    • Handle: RePEc:plo:pone00:0045863
    DOI: 10.1371/journal.pone.0045863
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    References listed on IDEAS

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    1. Guillaume Paré & Nancy R Cook & Paul M Ridker & Daniel I Chasman, 2010. "On the Use of Variance per Genotype as a Tool to Identify Quantitative Trait Interaction Effects: A Report from the Women's Genome Health Study," PLOS Genetics, Public Library of Science, vol. 6(6), pages 1-10, June.
    2. Katey J. Rayner & Christine C. Esau & Farah N. Hussain & Allison L. McDaniel & Stephanie M. Marshall & Janine M. van Gils & Tathagat D. Ray & Frederick J. Sheedy & Leigh Goedeke & Xueqing Liu & Oleg G, 2011. "Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides," Nature, Nature, vol. 478(7369), pages 404-407, October.
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