Integrated Genomic and Transcriptomic Study Reveals <i>MAPK11</i> and <i>PER1</i> as Important Obesity Susceptibility Genes in a High-Risk Hispanic/Latino Population
BACKGROUND: While GWAS (genome-wide association studies) have identified over 1000 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: ) followed by expression quantitative trait loci mapping and GWAS-expression quantitative trait loci colocalization. RESULTS: , linked to body mass index in females. Both genes play key roles in obesity-related pathways, including inflammation and circadian rhythm regulation. CONCLUSIONS: This integrative genomic-transcriptomic analysis uncovers 2 novel candidate genes for obesity and underscores the critical need for involving all populations and comprehensive adiposity measures in obesity research. By expanding beyond body mass index in a Hispanic/Latino population, we move closer to a deeper and more inclusive understanding of obesity's genetic architecture.
Authors
- Hannah G. Polikowsky (ORCID: https://orcid.org/0000-0001-7226-9752)
- Daeeun Kim (ORCID: https://orcid.org/0000-0002-9387-0739)
- Susan P. Fisher‐Hoch (ORCID: https://orcid.org/0000-0002-7894-5114)
- Faraz Bishehsari (ORCID: https://orcid.org/0000-0001-5644-2586)
- Joshua M. Landman (ORCID: https://orcid.org/0000-0003-2431-6053)
- Jennifer E Below (ORCID: https://orcid.org/0000-0002-1346-1872)
- Kristin L. Young (ORCID: https://orcid.org/0000-0003-0070-6145)
- Laura M. Raffield (ORCID: https://orcid.org/0000-0002-7892-193X)
- ABSALON D. GUTIERREZ
- Mariaelisa Graff (ORCID: https://orcid.org/0000-0001-6380-1735)
- Joseph B. McCormick (ORCID: https://orcid.org/0000-0002-5844-8102)
- Kari E. North (ORCID: https://orcid.org/0000-0002-8903-0366)
- Mohammad Yaser Anwar (ORCID: https://orcid.org/0000-0002-2349-8214)
- Sonja I. Berndt (ORCID: https://orcid.org/0000-0001-5230-0652)
- Joshua Arias (ORCID: https://orcid.org/0000-0001-6545-6656)
- Eitan Frankel (ORCID: https://orcid.org/0000-0003-2046-8500)
- Miryoung Lee (ORCID: https://orcid.org/0000-0003-4088-304X)
- Hung‐Hsin Chen (ORCID: https://orcid.org/0000-0002-1921-2797)
- Heather M. Highland (ORCID: https://orcid.org/0000-0002-3583-8239)
- Rashedeh Roshani (ORCID: https://orcid.org/0009-0001-2696-2852)
- Wanying Zhu (ORCID: https://orcid.org/0000-0002-2673-3048)
- Xinruo Zhang (ORCID: https://orcid.org/0000-0001-5789-4592)
- Yujie Wang (ORCID: https://orcid.org/0009-0000-9102-5497)
- Madeline G Gillman
- Victoria L Buchanan
- Mohanraj Krishnan
Institutions
- University of North Carolina at Chapel Hill (US)
- The University of Texas MD Anderson Cancer Center (US)
- Vanderbilt University (US)
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Nutrition Sciences (Belgium) (BE)
- Department of Health (ZA)
- The University of Texas Health Science Center (US)
- Department of Health and Human Services (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Circulation Genomic and Precision Medicine
- Published
- 2026-04-27
- DOI
- https://doi.org/10.1161/circgen.125.005298
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- American Heart Association
- National Institutes of Health
- National Human Genome Research Institute
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- Eunice Kennedy Shriver National Institute of Child Health and Human Development