Abstract 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 platform ToppGene, 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.

中文翻译：

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易患肥胖症的基因强调了保加利亚健康个体的 G 蛋白偶联受体相关通路

摘要 超重和肥胖是现代社会日益严重且日益严重的问题。它是许多慢性疾病的主要危险因素，包括 2 型糖尿病、心血管疾病和癌症。肥胖是由一系列遗传和环境因素相互作用导致的复杂疾病。本研究的目的是确定保加利亚健康个体易患肥胖症的遗传标记以及与肥胖症相关的分子途径。对两个 DNA 库进行了全外显子组测序：一个由 32 名保加利亚百岁老人和 61 名年轻健康个体中的一个组成，两者均具有正常的 BMI，并且对每个库估计了检测到的变异的等位基因频率。选择百岁老人是因为他们的外显子组可以被认为是健康和长寿的“黄金标准”，包括不含易导致肥胖的遗传变异。选择年轻人组是为了与百岁老人相比，可以评估青春期后易患肥胖症的变异。在数据库 DisGeNET 指定与肥胖相关的所有变体中，只有 17% 在研究的池中被发现。使用 ToppGene 平台，我们基于基因的变异确定了三个过度表达的途径，这些变异在年轻个体组中显示出等位基因频率的显着优势。这三个通路都是 G 蛋白偶联受体相关通路：GPCR 配体结合通路、G α (s) 信号事件通路和 A/1 类（视紫红质样受体）通路。