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

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; Tony Attwood; Belz Stephanie; Peter Braund; Jessy Brocheton; Jason Cooper; Abi Crisp-Hihn; Patrick Diemert; Nicola Foad; Tiphaine Godefroy; Jay Gracey; Emma Gray; Rhian Gwilliams; Susanne Heimerl; Jennifer Jolley; Unni Krishnan; Heather Lloyd-Jones; Ulrika Liljedahl; Ingrid Lugauer; Per Lundmark; Seraya Maouche; Jasbir S. Moore; Montalescot Gilles; David Muir; Elizabeth Murray; Chris P. Nelson; Jessica Neudert; David Niblett; Karen O'Leary; Helen Pollard; Carole Proust; Angela Rankin; Augusto Rendon; Catherine M. Rice; Hendrik Sager; Jennifer Sambrook; Schmitz Gerd; Michael Scholz; Laura Schroeder; Jonathan Stephens; Ann Christine Syvannen; Stefanie Tennstedt; Chris Wallace

doi:10.1371/journal.pone.0045863

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

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^*, Tony AttwoodBelz Stephanie, Peter Braund, Jessy Brocheton, Jason Cooper, Abi Crisp-Hihn, Patrick Diemert, Nicola Foad, Tiphaine Godefroy, Jay Gracey, Emma Gray, Rhian Gwilliams, Susanne Heimerl, Jennifer Jolley, Unni Krishnan, Heather Lloyd-Jones, Ulrika Liljedahl, Ingrid Lugauer, Per Lundmark, Seraya Maouche, Jasbir S. Moore, Montalescot Gilles, David Muir, Elizabeth Murray, Chris P. Nelson, Jessica Neudert, David Niblett, Karen O'Leary, Helen Pollard, Carole Proust, Angela Rankin, Augusto Rendon, Catherine M. Rice, Hendrik Sager, Jennifer Sambrook, Schmitz Gerd, Michael Scholz, Laura Schroeder, Jonathan Stephens, Ann Christine Syvannen, Stefanie Tennstedt, Chris Wallace

^*Corresponding author for this work

8 Citations (Scopus)

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.

Original language	English
Article number	e45863
Journal	PLoS ONE
Volume	7
Issue number	9
ISSN	1553-7390
DOIs	https://doi.org/10.1371/journal.pone.0045863
Publication status	Published - 21.09.2012

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10.1371/journal.pone.0045863

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Greliche, N., Zeller, T., Wild, P. S., Rotival, M., Schillert, A., Ziegler, A., Deloukas, P., Erdmann, J., Hengstenberg, C., Ouwehand, W. H., Samani, N. J., Schunkert, H., Munzel, T., Lackner, K. J., Cambien, F., Goodall, A. H., Tiret, L., Blankenberg, S., Trégouët, D. A., ... Wallace, C. (2012). Comprehensive Exploration of the Effects of miRNA SNPs on Monocyte Gene Expression. PLoS ONE, 7(9), Article e45863. https://doi.org/10.1371/journal.pone.0045863

@article{2f81ac2af18d4f989e2559d2905e1ee3,

title = "Comprehensive Exploration of the Effects of miRNA SNPs on Monocyte Gene Expression",

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.",

author = "Nicolas Greliche and Tanja Zeller and Wild, {Philipp S.} and Maxime Rotival and Arne Schillert and Andreas Ziegler and Panos Deloukas and Jeanette Erdmann and Christian Hengstenberg and Ouwehand, {Willem H.} and Samani, {Nilesh J.} and Heribert Schunkert and Thomas Munzel and Lackner, {Karl J.} and Fran{\c c}ois Cambien and Goodall, {Alison H.} and Laurence Tiret and Stefan Blankenberg and Tr{\'e}gou{\"e}t, {David Alexandre} and Tony Attwood and Belz Stephanie and Peter Braund and Jessy Brocheton and Jason Cooper and Abi Crisp-Hihn and Patrick Diemert and Nicola Foad and Tiphaine Godefroy and Jay Gracey and Emma Gray and Rhian Gwilliams and Susanne Heimerl and Jennifer Jolley and Unni Krishnan and Heather Lloyd-Jones and Ulrika Liljedahl and Ingrid Lugauer and Per Lundmark and Seraya Maouche and Moore, {Jasbir S.} and Montalescot Gilles and David Muir and Elizabeth Murray and Nelson, {Chris P.} and Jessica Neudert and David Niblett and Karen O'Leary and Helen Pollard and Carole Proust and Angela Rankin and Augusto Rendon and Rice, {Catherine M.} and Hendrik Sager and Jennifer Sambrook and Schmitz Gerd and Michael Scholz and Laura Schroeder and Jonathan Stephens and Syvannen, {Ann Christine} and Stefanie Tennstedt and Chris Wallace",

year = "2012",

month = sep,

day = "21",

doi = "10.1371/journal.pone.0045863",

language = "English",

volume = "7",

journal = "PLoS ONE",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "9",

}

Greliche, N, Zeller, T, Wild, PS, Rotival, M, Schillert, A, Ziegler, A, Deloukas, P, Erdmann, J, Hengstenberg, C, Ouwehand, WH, Samani, NJ, Schunkert, H, Munzel, T, Lackner, KJ, Cambien, F, Goodall, AH, Tiret, L, Blankenberg, S, Trégouët, DA, Attwood, T, Stephanie, B, Braund, P, Brocheton, J, Cooper, J, Crisp-Hihn, A, Diemert, P, Foad, N, Godefroy, T, Gracey, J, Gray, E, Gwilliams, R, Heimerl, S, Jolley, J, Krishnan, U, Lloyd-Jones, H, Liljedahl, U, Lugauer, I, Lundmark, P, Maouche, S, Moore, JS, Gilles, M, Muir, D, Murray, E, Nelson, CP, Neudert, J, Niblett, D, O'Leary, K, Pollard, H, Proust, C, Rankin, A, Rendon, A, Rice, CM, Sager, H, Sambrook, J, Gerd, S, Scholz, M, Schroeder, L, Stephens, J, Syvannen, AC, Tennstedt, S & Wallace, C 2012, 'Comprehensive Exploration of the Effects of miRNA SNPs on Monocyte Gene Expression', PLoS ONE, vol. 7, no. 9, e45863. https://doi.org/10.1371/journal.pone.0045863

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 - Attwood, Tony

AU - Stephanie, Belz

AU - Braund, Peter

AU - Brocheton, Jessy

AU - Cooper, Jason

AU - Crisp-Hihn, Abi

AU - Diemert, Patrick

AU - Foad, Nicola

AU - Godefroy, Tiphaine

AU - Gracey, Jay

AU - Gray, Emma

AU - Gwilliams, Rhian

AU - Heimerl, Susanne

AU - Jolley, Jennifer

AU - Krishnan, Unni

AU - Lloyd-Jones, Heather

AU - Liljedahl, Ulrika

AU - Lugauer, Ingrid

AU - Lundmark, Per

AU - Maouche, Seraya

AU - Moore, Jasbir S.

AU - Gilles, Montalescot

AU - Muir, David

AU - Murray, Elizabeth

AU - Nelson, Chris P.

AU - Neudert, Jessica

AU - Niblett, David

AU - O'Leary, Karen

AU - Pollard, Helen

AU - Proust, Carole

AU - Rankin, Angela

AU - Rendon, Augusto

AU - Rice, Catherine M.

AU - Sager, Hendrik

AU - Sambrook, Jennifer

AU - Gerd, Schmitz

AU - Scholz, Michael

AU - Schroeder, Laura

AU - Stephens, Jonathan

AU - Syvannen, Ann Christine

AU - Tennstedt, Stefanie

AU - Wallace, Chris

PY - 2012/9/21

Y1 - 2012/9/21

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.

UR - http://www.scopus.com/inward/record.url?scp=84866723307&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0045863

DO - 10.1371/journal.pone.0045863

M3 - Journal articles

C2 - 23029284

AN - SCOPUS:84866723307

SN - 1553-7390

VL - 7

JO - PLoS ONE

JF - PLoS ONE

IS - 9

M1 - e45863

ER -

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

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