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

A J Walley, P Jacobson, M Falchi, L Bottolo, J C Andersson, E Petretto, A Bonnefond, E Vaillant, C Lecoeur, V Vatin, M Jernas, D Balding, M Petteni, Y S Park, T Aitman, S Richardson, L Sjostrom, L M S Carlsson, P Froguel

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)137-47
Number of pages11
JournalInternational Journal of Obesity
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • 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

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