Genes predisposing to obesity emphasize G-protein coupled receptor associated pathways in healthy Bulgarian individuals

Overweight and obesity are serious and an ever-growing problem in modern society. It is a major risk factors for a number of chronic diseases, including type 2 diabetes, cardiovascular diseases and cancer. Obesity is a complex condition resulting from the interaction of a range of genetic and environmental factors. The aim of this study was to identify genetic markers predisposing to, and molecular pathways associated with, obesity in Bulgarian healthy individuals. Whole-exome sequencing was performed on two DNA pools: one constructed of 32 Bulgarian centenarians and one of 61 young healthy individuals, both with normal BMI, and allele frequencies of detected variants were estimated for each pool. Centenarians were chosen as their exome could be considered 'golden standard' for health and longevity, including being free of genetic variants predisposing to obesity. The young individuals group was chosen so variants predisposing to obesity after adolescence can be evaluated when compared to the centenarians. Of all variants designated to be associated with obesity by the database DisGeNET, only 17% were discovered in the studied pools. Using the platformToppGene, we identified three over-represented pathways based on genes with variants showing significant prelevance in allele frequency in the young individuals group. These three pathways were all G-protein coupled receptor associated pathways: the GPCR ligand binding pathway, the G alpha (s) signalling events pathway and the Class A/1 (Rhodopsin-like receptors) pathway. Understanding the genetic etiology of obesity in different populations is instrumental in developing pharmacological targets for population-specific obesity therapies.