Unraveling the Genetic Architecture of Obesity: A Path to Personalized Medicine

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 vari...

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Main Authors: Faisal Kunnathodi, Amr A. Arafat, Waleed Alhazzani, Mohammad Mustafa, Sarfuddin Azmi, Ishtiaque Ahmad, Jamala Saleh Selan, Riyasdeen Anvarbatcha, Haifa F. Alotaibi
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/15/12/1482
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author Faisal Kunnathodi
Amr A. Arafat
Waleed Alhazzani
Mohammad Mustafa
Sarfuddin Azmi
Ishtiaque Ahmad
Jamala Saleh Selan
Riyasdeen Anvarbatcha
Haifa F. Alotaibi
author_facet Faisal Kunnathodi
Amr A. Arafat
Waleed Alhazzani
Mohammad Mustafa
Sarfuddin Azmi
Ishtiaque Ahmad
Jamala Saleh Selan
Riyasdeen Anvarbatcha
Haifa F. Alotaibi
author_sort Faisal Kunnathodi
collection DOAJ
description 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 <i>FTO</i> and <i>MC4R</i> 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.
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spelling doaj-art-a60f4a82aecf4c8a9ba5c2319e777c5d2025-08-20T02:24:38ZengMDPI AGDiagnostics2075-44182025-06-011512148210.3390/diagnostics15121482Unraveling the Genetic Architecture of Obesity: A Path to Personalized MedicineFaisal Kunnathodi0Amr A. Arafat1Waleed Alhazzani2Mohammad Mustafa3Sarfuddin Azmi4Ishtiaque Ahmad5Jamala Saleh Selan6Riyasdeen Anvarbatcha7Haifa F. Alotaibi8Health Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaHealth Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaHealth Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaHealth Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaHealth Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaHealth Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaHealth Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaHealth Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaHealth Research Center, Ministry of Defense Health Services, Riyadh 12485, Saudi ArabiaObesity 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 <i>FTO</i> and <i>MC4R</i> 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.https://www.mdpi.com/2075-4418/15/12/1482obesity treatmentpersonalized medicinegenomicsgenome-wide association studies (GWAS)epigenetics
spellingShingle Faisal Kunnathodi
Amr A. Arafat
Waleed Alhazzani
Mohammad Mustafa
Sarfuddin Azmi
Ishtiaque Ahmad
Jamala Saleh Selan
Riyasdeen Anvarbatcha
Haifa F. Alotaibi
Unraveling the Genetic Architecture of Obesity: A Path to Personalized Medicine
Diagnostics
obesity treatment
personalized medicine
genomics
genome-wide association studies (GWAS)
epigenetics
title Unraveling the Genetic Architecture of Obesity: A Path to Personalized Medicine
title_full Unraveling the Genetic Architecture of Obesity: A Path to Personalized Medicine
title_fullStr Unraveling the Genetic Architecture of Obesity: A Path to Personalized Medicine
title_full_unstemmed Unraveling the Genetic Architecture of Obesity: A Path to Personalized Medicine
title_short Unraveling the Genetic Architecture of Obesity: A Path to Personalized Medicine
title_sort unraveling the genetic architecture of obesity a path to personalized medicine
topic obesity treatment
personalized medicine
genomics
genome-wide association studies (GWAS)
epigenetics
url https://www.mdpi.com/2075-4418/15/12/1482
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