Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression
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Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression. / Greliche, Nicolas; Zeller, Tanja; Wild, Philipp S; Rotival, Maxime; Schillert, Arne; Ziegler, Andreas; Deloukas, Panos; Erdmann, Jeanette; Hengstenberg, Christian; Ouwehand, Willem H; Samani, Nilesh J; Schunkert, Heribert; Munzel, Thomas; Lackner, Karl J; Cambien, François; Goodall, Alison H; Tiret, Laurence; Blankenberg, Stefan; Trégouët, David-Alexandre; CardioGenics Consortium.
in: PLOS ONE, Jahrgang 7, Nr. 9, 2012, S. e45863.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression
AU - Greliche, Nicolas
AU - Zeller, Tanja
AU - Wild, Philipp S
AU - Rotival, Maxime
AU - Schillert, Arne
AU - Ziegler, Andreas
AU - Deloukas, Panos
AU - Erdmann, Jeanette
AU - Hengstenberg, Christian
AU - Ouwehand, Willem H
AU - Samani, Nilesh J
AU - Schunkert, Heribert
AU - Munzel, Thomas
AU - Lackner, Karl J
AU - Cambien, François
AU - Goodall, Alison H
AU - Tiret, Laurence
AU - Blankenberg, Stefan
AU - Trégouët, David-Alexandre
AU - CardioGenics Consortium
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - 3' Untranslated Regions
KW - Adult
KW - Aged
KW - Case-Control Studies
KW - Coronary Artery Disease/genetics
KW - Female
KW - Gene Expression
KW - Genome-Wide Association Study
KW - Humans
KW - Leukocytes, Mononuclear/metabolism
KW - Linear Models
KW - Linkage Disequilibrium
KW - Male
KW - MicroRNAs/genetics
KW - Middle Aged
KW - Oligonucleotide Array Sequence Analysis
KW - Polymorphism, Single Nucleotide
KW - RNA Interference
KW - Transcriptome
U2 - 10.1371/journal.pone.0045863
DO - 10.1371/journal.pone.0045863
M3 - SCORING: Journal article
C2 - 23029284
VL - 7
SP - e45863
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 9
ER -