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Genetics and Epigenetics

Genetic impact of central adiposity on systolic blood pressure in females: interaction and mediation by TG/HDL-C, HbA1c, and uric acid across BMI categories

International Journal of Obesity (2025)Cite this article

Subjects

Abstract

Background

Genetic predisposition to central adiposity is associated with metabolic dysfunction and obesity-related hypertension. This study investigated the association between genetic predisposition of general and central adiposity and systolic blood pressure (SBP) across body mass index (BMI) categories. Additionally, we explored whether, among females, the metabolic factors, triglyceride-to-HDL cholesterol (TG/HDL-C) ratio, glycated hemoglobin (HbA1c), and serum uric acid (SUA), modulate these relationships.

Methods

This cross-sectional study included 10,734 females from the Taiwan Biobank. Associations between polygenic score of body mass index (PGS-BMI), waist-circumference (PGS-WC), waist to hip ratio (PGS-WHR), waist to height ratio (PGS-WHtR) and SBP were assessed using multivariable generalized additive models (GAM). The strongest PGS was further examined for interaction and mediation effects with metabolic factors across BMI categories. Polygenic pathway analyses were also conducted to identify underlying biological mechanisms.

Results

Among the four PGSs, PGS-WC showed the strongest association with SBP, particularly in females with normal weight (β = 0.026, 95% CI: 0.002–0.050; p_linear = 0.033; effective degree of freedom (edf) = 1.063; F = 3.201; p_smooth = 0.060) and overweight (β = –0.058, 95% CI: –0.095 to –0.021; p_linear = 0.002; edf = 2.272; F = 4.073; p_smooth = 0.006). The TG/HDL-C ratio significantly modulated this association across normal weight, overweight, and obesity categories in both interaction and mediation analyses. Polygenic pathway implicated biological processes including signal transduction, metabolism, immune regulation, and DNA repair.

Conclusion

These findings underscore the genetic influence of central adiposity on SBP regulation, particularly among females with normal weight and overweight. The TG/HDL-C ratio plays a key role in modulating this relationship, suggesting that metabolic risk-targeted interventions may enhance hypertension prevention and management in genetically susceptible populations.

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Fig. 1: Interaction analysis of PGS-WC and metabolic factors on systolic blood pressure (SBP) across BMI categories.
Fig. 2: Stratified mediation effects of PGS-WC on systolic blood pressure via waist circumference and metabolic factors across BMI categories.
Fig. 3: Polygenic pathways of waist circumference (PP-WC) influencing SBP via waist circumference and TG/HDL-C ratio across BMI categories.

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Data availability

The data that support the findings of this study are available from Taiwan Biobank, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission from Taiwan Biobank. GWAS summary statistics for central adiposity had been submitted to the National Human Genome Research Institute—European Bioinformatics Institute (NHGRI-EBI) catalog with accession numbers GCST 90572795 for BMI, GCST 90572792 for WC, GSCT 90572793 for WHR, and GCST 90572794 for WHtR.

Code availability

The corresponding author (baich@tmu.edu.tw) will provide the codes used in this study upon request.

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Acknowledgements

The authors express their sincere gratitude to Yen-Chun Fan (Department of Allied Health Education and Digital Learning, College of Nursing, National Taipei University of Nursing and Health Sciences) and Shang-Hao Wu (College of Public Health, Taipei Medical University) for their valuable contributions to this study. This research was supported by the National Science and Technology Council of Taiwan through Grant NSTC 113-2314-B-038-080-MY3.

Author information

Authors and Affiliations

  1. International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Rizki Amalia Gumilang

  2. Academic Hospital & Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

    Rizki Amalia Gumilang

  3. Department of Public Health, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Chyi-Huey Bai

  4. School of Public Health, College of Public Health, Taipei Medical University, New Taipei, Taiwan

    Chyi-Huey Bai

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  1. Rizki Amalia Gumilang
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Contributions

RAG contributed to the study design and methodology development, data analysis and interpretation of the results and wrote and approved the manuscript. CHB constructed the study design and analytical concept, obtained funding, and analyzed, critically revised, and approved the manuscript. All the authors have read and approved the final manuscript.

Corresponding author

Correspondence to Chyi-Huey Bai.

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The authors declare no competing interests.

Ethics approval and consent to participate

Ethical clearance for this study was granted by the Institutional Board Review of Taipei Medical University, with the approval number N202104112. All individuals participating in the Taiwan Biobank provided informed consent before enrolling in the study. Data were retrieved and analyzed in accordance with Taiwan Biobank data safety regulations. This study was conducted in compliance with the STrengthening the REporting of Genetic Association Studies (STREGA) guidelines (see STREGA checklist in the Supplementary Materials).

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Gumilang, R.A., Bai, CH. Genetic impact of central adiposity on systolic blood pressure in females: interaction and mediation by TG/HDL-C, HbA1c, and uric acid across BMI categories. Int J Obes (2025). https://doi.org/10.1038/s41366-025-01917-z

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