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

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; plinear = 0.033; effective degree of freedom (edf) = 1.063; F = 3.201; psmooth = 0.060) and overweight (β = 0.058, 95 CI: 0.095 to 0.021; plinear = 0.002; edf = 2.272; F = 4.073; psmooth = 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. © The Author(s), under exclusive licence to Springer Nature Limited 2025.