Exploring genetic susceptibility to obesity through genome functional pathway analysis.

Abstract

Obesity has been reaching epidemic levels in recent decades, with a growing body of research identifying predisposing genetic components. To explore the relationship of genetic factors contributing to obesity, an analytical computer-based gene-profiling approach utilizing an updated list of clinically relevant and known obesity-related genes was undertaken. An updated list of 494 genes reportedly associated with obesity was compiled, and the GeneAnalytics profiling software was utilized to interrogate genomic databases from GeneCards® to cross-reference obesity gene sets against tissues and cells, diseases, genetic pathways, gene ontology (GO)-biological processes and GO-molecular functions, phenotypes, and compounds. Obesity-related fields identified by GeneAnalytics algorithms included 8 diseases, 46 pathways, 62 biological processes, 22 molecular functions, 148 phenotypes, and 286 compounds impacting adipogenesis, signal transduction by G-protein coupled receptors, and lipid metabolism involving insulin-related genes (IGF1, INS, IRS1). GO-biological processes identified feeding behavior, cholesterol metabolic process, and glucose and cholesterol homeostasis pathways, while GO-molecular processes pertained to receptor binding, affecting glucose homeostasis, body weight, and circulating insulin and triglyceride levels. The gene-profiling model suggests that pathogenesis of obesity relates to the coordination of biological responses to glucose and intracellular lipids possibly through a disruption of biochemical cascades and cellular signaling arising from affected receptors.