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 language | English |
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Pages (from-to) | 137-147 |
Number of pages | 11 |
Journal | International Journal of Obesity |
Volume | 36 |
Issue number | 1 |
Early online date | 22 Mar 2011 |
DOIs | |
Publication status | Published - 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