Differential coexpression analysis of obesity-associated networks in human subcutaneous adipose tissue

Title: Differential coexpression analysis of obesity-associated networks in human subcutaneous adipose tissue
Authors: Walley, AJ
Jacobson, P
Falchi, M
Bottolo, L
Andersson, JC
Petretto, E
Bonnefond, A
Vaillant, E
Lecoeur, C
Vatin, V
Jernas, M
Balding, D
Petteni, M
Park, YS
Aitman, T
Richardson, S
Sjostrom, L
Carlsson, LMS
Froguel, P
Item Type: Journal Article
Abstract: Objective: To use a unique obesity-discordant sib-pair study design to combine differential expression analysis, expression quantitative trait loci (eQTLs) mapping and a coexpression regulatory network approach in subcutaneous human adipose tissue to identify genes relevant to the obese state. Study design: Genome-wide transcript expression in subcutaneous human adipose tissue was measured using Affymetrix U133 Plus 2.0 microarrays (Affymetrix, Santa Clara, CA, USA), and genome-wide genotyping data was obtained using an Applied Biosystems (Applied Biosystems; Life Technologies, Carlsbad, CA, USA) SNPlex linkage panel. Subjects: A total of 154 Swedish families ascertained through an obese proband (body mass index (BMI) >30 kg m−2) with a discordant sibling (BMI>10 kg m−2 less than proband). Results: Approximately one-third of the transcripts were differentially expressed between lean and obese siblings. The cellular adhesion molecules (CAMs) KEGG grouping contained the largest number of differentially expressed genes under cis-acting genetic control. By using a novel approach to contrast CAMs coexpression networks between lean and obese siblings, a subset of differentially regulated genes was identified, with the previously GWAS obesity-associated neuronal growth regulator 1 (NEGR1) as a central hub. Independent analysis using mouse data demonstrated that this finding of NEGR1 is conserved across species. Conclusion: Our data suggest that in addition to its reported role in the brain, NEGR1 is also expressed in subcutaneous adipose tissue and acts as a central ‘hub’ in an obesity-related transcript network.
Issue Date: 22-Mar-2011
Date of Acceptance: 7-Jan-2011
URI: http://hdl.handle.net/10044/1/57216
DOI: https://dx.doi.org/10.1038/ijo.2011.22
ISSN: 0307-0565
Publisher: Nature Publishing Group
Start Page: 137
End Page: 147
Journal / Book Title: International Journal of Obesity
Volume: 36
Issue: 1
Copyright Statement: © 2012 Macmillan Publishers Limited. All rights reserved.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: G0600609
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Nutrition & Dietetics
gene expression
network
eQTL
sibpair
linkage
adipose tissue
GENOME-WIDE ASSOCIATION
GENE-EXPRESSION
LINKAGE ANALYSIS
MOLECULAR NETWORKS
MICROARRAY DATA
EARLY-ONSET
FAT MASS
DISEASE
TRAIT
LOCI
Adolescent
Adult
Animals
Body Mass Index
Cell Adhesion Molecules
Cell Adhesion Molecules, Neuronal
Cohort Studies
Female
GPI-Linked Proteins
Gene Expression Regulation
Genetic Linkage
Genome-Wide Association Study
Humans
Male
Middle Aged
Obesity
Protein Array Analysis
Quantitative Trait Loci
Real-Time Polymerase Chain Reaction
Siblings
Subcutaneous Fat
Sweden
Thinness
Young Adult
11 Medical And Health Sciences
13 Education
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Department of Medicine
Faculty of Medicine
Faculty of Natural Sciences
Epidemiology, Public Health and Primary Care



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