Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes.
Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and...
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2012-01-01
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doaj-48c00fdd38354c18b5237e49bea1cf972020-11-25T01:52:30ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-0182e100250510.1371/journal.pgen.1002505Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes.Josine L MinGeorge NicholsonIngileif HalgrimsdottirKristian AlmstrupAndreas PetriAmy BarrettMary TraversNigel W RaynerReedik MägiFredrik H PetterssonJohn BroxholmeMatt J NevilleQuin F WillsJane CheesemanGIANT ConsortiumMolPAGE ConsortiumMaxine AllenChris C HolmesTim D SpectorJan FlecknerMark I McCarthyFredrik KarpeCecilia M LindgrenKrina T ZondervanMetabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS-associated modules of coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed in ABD or GLU, 685 (7.6%) were expressed in ABD and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (D(ABD-GLU) = 0.89), seven of which were associated with MetS (FDR P<0.01). The strongest associated module, significantly enriched for immune response-related processes, contained 94/620 (15%) genes with inter-depot differences. In an independent cohort of 145/141 twins with ABD and WB longitudinal expression data, median variability in ABD due to familiality was greater for MetS-associated versus un-associated modules (ABD: 0.48 versus 0.18, P = 0.08; GLU: 0.54 versus 0.20, P = 7.8×10(-4)). Cis-eQTL analysis of probesets associated with MetS (FDR P<0.01) and/or inter-depot differences (FDR P<0.01) provided evidence for 32 eQTLs. Corresponding eSNPs were tested for association with MetS-related phenotypes in two GWAS of >100,000 individuals; rs10282458, affecting expression of RARRES2 (encoding chemerin), was associated with body mass index (BMI) (P = 6.0×10(-4)); and rs2395185, affecting inter-depot differences of HLA-DRB1 expression, was associated with high-density lipoprotein (P = 8.7×10(-4)) and BMI-adjusted waist-to-hip ratio (P = 2.4×10(-4)). Since many genes and their interactions influence complex traits such as MetS, integrated analysis of genotypes and coexpression networks across multiple tissues relevant to clinical traits is an efficient strategy to identify novel associations.http://europepmc.org/articles/PMC3285582?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Josine L Min George Nicholson Ingileif Halgrimsdottir Kristian Almstrup Andreas Petri Amy Barrett Mary Travers Nigel W Rayner Reedik Mägi Fredrik H Pettersson John Broxholme Matt J Neville Quin F Wills Jane Cheeseman GIANT Consortium MolPAGE Consortium Maxine Allen Chris C Holmes Tim D Spector Jan Fleckner Mark I McCarthy Fredrik Karpe Cecilia M Lindgren Krina T Zondervan |
spellingShingle |
Josine L Min George Nicholson Ingileif Halgrimsdottir Kristian Almstrup Andreas Petri Amy Barrett Mary Travers Nigel W Rayner Reedik Mägi Fredrik H Pettersson John Broxholme Matt J Neville Quin F Wills Jane Cheeseman GIANT Consortium MolPAGE Consortium Maxine Allen Chris C Holmes Tim D Spector Jan Fleckner Mark I McCarthy Fredrik Karpe Cecilia M Lindgren Krina T Zondervan Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. PLoS Genetics |
author_facet |
Josine L Min George Nicholson Ingileif Halgrimsdottir Kristian Almstrup Andreas Petri Amy Barrett Mary Travers Nigel W Rayner Reedik Mägi Fredrik H Pettersson John Broxholme Matt J Neville Quin F Wills Jane Cheeseman GIANT Consortium MolPAGE Consortium Maxine Allen Chris C Holmes Tim D Spector Jan Fleckner Mark I McCarthy Fredrik Karpe Cecilia M Lindgren Krina T Zondervan |
author_sort |
Josine L Min |
title |
Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. |
title_short |
Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. |
title_full |
Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. |
title_fullStr |
Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. |
title_full_unstemmed |
Coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. |
title_sort |
coexpression network analysis in abdominal and gluteal adipose tissue reveals regulatory genetic loci for metabolic syndrome and related phenotypes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2012-01-01 |
description |
Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS-associated modules of coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed in ABD or GLU, 685 (7.6%) were expressed in ABD and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (D(ABD-GLU) = 0.89), seven of which were associated with MetS (FDR P<0.01). The strongest associated module, significantly enriched for immune response-related processes, contained 94/620 (15%) genes with inter-depot differences. In an independent cohort of 145/141 twins with ABD and WB longitudinal expression data, median variability in ABD due to familiality was greater for MetS-associated versus un-associated modules (ABD: 0.48 versus 0.18, P = 0.08; GLU: 0.54 versus 0.20, P = 7.8×10(-4)). Cis-eQTL analysis of probesets associated with MetS (FDR P<0.01) and/or inter-depot differences (FDR P<0.01) provided evidence for 32 eQTLs. Corresponding eSNPs were tested for association with MetS-related phenotypes in two GWAS of >100,000 individuals; rs10282458, affecting expression of RARRES2 (encoding chemerin), was associated with body mass index (BMI) (P = 6.0×10(-4)); and rs2395185, affecting inter-depot differences of HLA-DRB1 expression, was associated with high-density lipoprotein (P = 8.7×10(-4)) and BMI-adjusted waist-to-hip ratio (P = 2.4×10(-4)). Since many genes and their interactions influence complex traits such as MetS, integrated analysis of genotypes and coexpression networks across multiple tissues relevant to clinical traits is an efficient strategy to identify novel associations. |
url |
http://europepmc.org/articles/PMC3285582?pdf=render |
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