Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.

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 × 3ut...

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Main Authors: Nicolas Greliche, Tanja Zeller, Philipp S Wild, Maxime Rotival, Arne Schillert, Andreas Ziegler, Cardiogenics Consortium, 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0045863&type=printable
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author Nicolas Greliche
Tanja Zeller
Philipp S Wild
Maxime Rotival
Arne Schillert
Andreas Ziegler
Cardiogenics Consortium
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
author_facet Nicolas Greliche
Tanja Zeller
Philipp S Wild
Maxime Rotival
Arne Schillert
Andreas Ziegler
Cardiogenics Consortium
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
author_sort Nicolas Greliche
collection DOAJ
description 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.
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spelling doaj-art-e3be40b95d2248a8b4fe1aa39ef3e2c02025-08-20T02:05:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4586310.1371/journal.pone.0045863Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.Nicolas GrelicheTanja ZellerPhilipp S WildMaxime RotivalArne SchillertAndreas ZieglerCardiogenics ConsortiumPanos DeloukasJeanette ErdmannChristian HengstenbergWillem H OuwehandNilesh J SamaniHeribert SchunkertThomas MunzelKarl J LacknerFrançois CambienAlison H GoodallLaurence TiretStefan BlankenbergDavid-Alexandre TrégouëtWe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0045863&type=printable
spellingShingle Nicolas Greliche
Tanja Zeller
Philipp S Wild
Maxime Rotival
Arne Schillert
Andreas Ziegler
Cardiogenics Consortium
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
Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.
PLoS ONE
title Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.
title_full Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.
title_fullStr Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.
title_full_unstemmed Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.
title_short Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.
title_sort comprehensive exploration of the effects of mirna snps on monocyte gene expression
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0045863&type=printable
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