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

OBJECTIVE: To use a unique obesity-discordant sib-pair study design to combine differential expression analysis, expression quantitative trait loci (eQTLs) mapping, and a co-expression 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+2.0 microarrays and genomewide genotyping data was obtained using an Applied Biosystems SNPlex linkage panel. SUBJECTS: 154 Swedish families ascertained through an obese proband (Body Mass Index >30kg/m(2)) with a discordant sibling (BMI>10kg/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 co-expression networks between lean and obese siblings, a subset of differentially regulated genes was identified, with the previously GWAS obesity-associated NEGR1 as a central hub. Independent analysis using mouse data demonstrated that this finding for NEGR1 is conserved across species. CONCLUSION: Our data suggests 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.