Integrated Genomic and Transcriptomic Study Reveals MAPK11 and PER1 as Important Obesity Susceptibility Genes in a High-risk Hispanic/Latino Population

Background: While genome-wide association studies (GWAS) have identified over 1,000 obesity-associated loci, their functional impact on gene expression remains unclear. Moreover, many studies have not fully captured the genetic architecture of obesity in high-risk populations or considered the complexity of adiposity beyond traditional measures. To address these gaps, this study explores the genetic and transcriptomic pathways of obesity using diverse obesity phenotypes in a high-risk population. Methods: We analyzed genomic and whole blood transcriptomic data from the Cameron County Hispanic Cohort (CCHC), performing GWAS on 13 obesity-related traits. Differential expression (DE) analysis was conducted for genes near GWAS-identified SNPs (p < 5x10−6) followed by expression quantitative trait loci (eQTL) mapping and GWAS-eQTL colocalization. Results: GWAS identified 486 trait associations, including six genome-wide significant (p < 5×10−8) loci, with three novel signals linked to abdominal subcutaneous adipose tissue (SAT), body fat percent, and waist circumference. Among 3024 genes near these loci, 60 showed differential expression. Further eQTL analysis suggested two SNP-gene-trait relationships: rs543314376-MAPK11, associated with SAT volume in females, and rs963018484-PER1, linked to BMI in females. Both genes play key roles in obesity related pathways, including inflammation and circadian rhythm regulation. Conclusions: This integrative genomic-transcriptomic analysis uncovers two novel candidate genes for obesity and underscores the critical need for involving all populations and comprehensive adiposity measures in obesity research. By expanding beyond BMI in a Hispanic/Latino population, we move closer to a deeper and more inclusive understanding of obesity’s genetic architecture.

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UNC Libraries
Published
2026-10-28
DOI
https://doi.org/10.17615/ggp5-e589
Primary Topic
Genetic Associations and Epidemiology
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article
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article

Integrated Genomic and Transcriptomic Study Reveals MAPK11 and PER1 as Important Obesity Susceptibility Genes in a High-risk Hispanic/Latino Population

Hannah G. Polikowsky, Susan P. Fisher‐Hoch, Absalon Gutierrez, Joshua M. Landman et al.
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UNC Libraries
Genetic Associations and Epidemiology
article

Integrated Genomic and Transcriptomic Study Reveals MAPK11 and PER1 as Important Obesity Susceptibility Genes in a High-risk Hispanic/Latino Population

Hannah G. Polikowsky, Susan P. Fisher‐Hoch, Absalon Gutierrez, Joshua M. Landman, Kristin L. Young, Laura M. Raffield, Mariaelisa Graff, Victoria L. Buchanan, Kari E. North, Mohammad Yaser Anwar, Sonja I. Berndt, Joshua D. Arias, Miryoung Lee, Hung‐Hsin Chen, Heather M. Highland, Rashedeh Roshani, Mohanraj Krishnan, Madeline G Gillman, Joseph B McCormick, Jennifer E Below, Elizabeth G. Frankel, Daeeun Kim, Xinruo Zhang, Yujie Wang, Faraz Bishehsari, Wanying Zhu
article en

Abstract

Background: While genome-wide association studies (GWAS) have identified over 1,000 obesity-associated loci, their functional impact on gene expression remains unclear. Moreover, many studies have not fully captured the genetic architecture of obesity in high-risk populations or considered the complexity of adiposity beyond traditional measures. To address these gaps, this study explores the genetic and transcriptomic pathways of obesity using diverse obesity phenotypes in a high-risk population. Methods: We analyzed genomic and whole blood transcriptomic data from the Cameron County Hispanic Cohort (CCHC), performing GWAS on 13 obesity-related traits. Differential expression (DE) analysis was conducted for genes near GWAS-identified SNPs (p < 5x10−6) followed by expression quantitative trait loci (eQTL) mapping and GWAS-eQTL colocalization. Results: GWAS identified 486 trait associations, including six genome-wide significant (p < 5×10−8) loci, with three novel signals linked to abdominal subcutaneous adipose tissue (SAT), body fat percent, and waist circumference. Among 3024 genes near these loci, 60 showed differential expression. Further eQTL analysis suggested two SNP-gene-trait relationships: rs543314376-MAPK11, associated with SAT volume in females, and rs963018484-PER1, linked to BMI in females. Both genes play key roles in obesity related pathways, including inflammation and circadian rhythm regulation. Conclusions: This integrative genomic-transcriptomic analysis uncovers two novel candidate genes for obesity and underscores the critical need for involving all populations and comprehensive adiposity measures in obesity research. By expanding beyond BMI in a Hispanic/Latino population, we move closer to a deeper and more inclusive understanding of obesity’s genetic architecture.

UNC Libraries
University of North Carolina at Chapel Hill (US)
Simons Foundation, Welch Foundation, American Heart Association, Knights Templar Eye Foundation, Research to Prevent Blindness, Maryland Industrial Partnerships, Center for Strategic Scientific Initiatives, National Cancer Institute, King’s College London, South London and Maudsley NHS Foundation Trust, Wellcome Trust, New York University Abu Dhabi, British Heart Foundation, Leverhulme Trust, Department of Health and Social Care, Royal Society, Heart Research UK, Academy of Medical Sciences, Royal Society of Chemistry, University of Oxford, European Commission, Rosetrees Trust, European Cooperation in Science and Technology, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Natural Science Foundation of China, Bundesministerium für Bildung und Forschung, Ministry of Higher Education, Malaysia, Ministero della Salute, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Ministero dell’Istruzione, dell’Università e della Ricerca, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Magyar Tudományos Akadémia, Karolinska Institutet, Vetenskapsrådet, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Natural Science Foundation of Shandong Province, Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg, Novo Nordisk Fonden, CAS-Croucher Funding Scheme for Joint Laboratories, Nasjonalforeningen for Folkehelsen, Ministerie van Economische Zaken en Klimaat, Fondation ISREC, Zhongshan Science and Technology Bureau, National Science and Technology Major Project, Institute for Healthcare Policy and Innovation, University of Michigan, NIHR Maudsley Biomedical Research Centre, Natural Sciences and Engineering Research Council of Canada, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council, Science and Engineering Research Board, Comisión Sectorial de Investigación Científica, Sunway University, National Key Research and Development Program of China, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Nursing Research, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Institute of Dental and Craniofacial Research, Division of Materials Research, Division of Civil, Mechanical and Manufacturing Innovation, National Center for Advancing Translational Sciences, Core Research for Evolutional Science and Technology, H2020 European Research Council, H2020 Future and Emerging Technologies, Division of Diabetes, Endocrinology, and Metabolic Diseases, Natural Science Foundation of Zhejiang Province, H2020 LEIT Information and Communication Technologies
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