Kunnathodi Faisal, Arafat Amr A, Alhazzani Waleed, Mustafa Mohammad, Azmi Sarfuddin, Ahmad Ishtiaque, Selan Jamala Saleh, Anvarbatcha Riyasdeen, Alotaibi Haifa F
Health Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi Arabia.
Departments of Adult Cardiac Surgery, Prince Sultan Cardiac Center, Riyadh 31982, Saudi Arabia.
Diagnostics (Basel). 2025 Jun 11;15(12):1482. doi: 10.3390/diagnostics15121482.
Obesity is a global health challenge characterized by significant heterogeneity in causes and treatment responses, complicating sustainable management. This narrative review explores the genomic architecture of obesity and its implications for personalized interventions, focusing on how genetic variations influence key biological pathways and treatment outcomes. A comprehensive literature search, guided by the authors' expertise, was conducted to identify key publications on the genomics of obesity and personalized approaches. The selection of articles prioritized those that provided direct insights into the genomic basis of obesity and its potential for informing tailored strategies. Genomic studies reveal both monogenic and polygenic influences on obesity, identifying numerous susceptibility loci. Genome-wide association studies (GWASs) have linked common variants in genes like and to increased BMI and appetite dysregulation, respectively. Epigenetic research highlights the role of DNA methylation and other modifications in gene-environment interactions. Genetic and polygenic risk scores (GRSs and PRSs) show potential for refining risk stratification and predicting treatment response. The gut microbiome and metabolome also contribute to obesity pathogenesis, offering novel targets for intervention. Personalized medicine offers significant potential for improving obesity management through tailored interventions based on an individual's genetic and 'omics' profile. Future research should focus on elucidating the functional consequences of identified variants, exploring gene-environment interactions, and developing strategies to overcome current limitations in clinical translation. With continued advancements, precision medicine can enhance treatment efficacy, increase sustainability, and help reduce the global burden of obesity-related diseases.
肥胖是一项全球性的健康挑战，其病因和治疗反应存在显著异质性，这使得可持续管理变得复杂。本叙述性综述探讨了肥胖的基因组结构及其对个性化干预的影响，重点关注基因变异如何影响关键生物学途径和治疗结果。在作者专业知识的指导下，进行了全面的文献检索，以确定有关肥胖基因组学和个性化方法的关键出版物。文章的选择优先考虑那些能直接洞察肥胖的基因组基础及其为定制策略提供信息的潜力的研究。基因组研究揭示了单基因和多基因对肥胖的影响，确定了众多易感基因座。全基因组关联研究（GWAS）已将 等基因中的常见变异分别与体重指数（BMI）增加和食欲失调联系起来。表观遗传学研究强调了DNA甲基化和其他修饰在基因 - 环境相互作用中的作用。遗传和多基因风险评分（GRS和PRS）显示出改善风险分层和预测治疗反应的潜力。肠道微生物组和代谢组也对肥胖发病机制有影响，为干预提供了新靶点。个性化医学通过基于个体的遗传和“组学”特征进行定制干预，在改善肥胖管理方面具有巨大潜力。未来的研究应侧重于阐明已识别变异的功能后果，探索基因 - 环境相互作用，并制定策略克服临床转化中的当前限制。随着不断进步，精准医学可以提高治疗效果，增强可持续性，并有助于减轻肥胖相关疾病的全球负担。
