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Open Access Highly Accessed Research article

Gene expression profiling in whole blood identifies distinct biological pathways associated with obesity

Sujoy Ghosh1*, Robert Dent2, Mary-Ellen Harper3, Shelby A Gorman4, Joan S Stuart4 and Ruth McPherson5*

Author Affiliations

1 Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, USA

2 Ottawa Hospital Weight Management Clinic, Ottawa Hospital, Ottawa, Canada

3 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada

4 GlaxoSmithKline, Research Triangle Park, USA

5 University of Ottawa Heart Institute, Ottawa, Canada

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BMC Medical Genomics 2010, 3:56  doi:10.1186/1755-8794-3-56

Published: 1 December 2010

Abstract

Background

Obesity is reaching epidemic proportions and represents a significant risk factor for cardiovascular disease, diabetes, and cancer.

Methods

To explore the relationship between increased body mass and gene expression in blood, we conducted whole-genome expression profiling of whole blood from seventeen obese and seventeen well matched lean subjects. Gene expression data was analyzed at the individual gene and pathway level and a preliminary assessment of the predictive value of blood gene expression profiles in obesity was carried out.

Results

Principal components analysis of whole-blood gene expression data from obese and lean subjects led to efficient separation of the two cohorts. Pathway analysis by gene-set enrichment demonstrated increased transcript levels for genes belonging to the "ribosome", "apoptosis" and "oxidative phosphorylation" pathways in the obese cohort, consistent with an altered metabolic state including increased protein synthesis, enhanced cell death from proinflammatory or lipotoxic stimuli, and increased energy demands. A subset of pathway-specific genes acted as efficient predictors of obese or lean class membership when used in Naive Bayes or logistic regression based classifiers.

Conclusion

This study provides a comprehensive characterization of the whole blood transcriptome in obesity and demonstrates that the investigation of gene expression profiles from whole blood can inform and illustrate the biological processes related to regulation of body mass. Additionally, the ability of pathway-related gene expression to predict class membership suggests the feasibility of a similar approach for identifying clinically useful blood-based predictors of weight loss success following dietary or surgical interventions.