Development of a Sex-Specific Prevalent Hypertension Discrimination Model in Korean Adults Using Genetic Risk Scores...

Genetic and metabolic factors contribute to hypertension, yet integrated sex-specific models remain limited. In this cross-sectional study, we developed sex-specific models to discriminate prevalent hypertension discrimination by integrating genetic risk scores (GRSs) with metabolic and vascular biomarkers. From 2075 Korean adults, the final models were evaluated using model-specific complete-case datasets (total n = 775; males n = 382; females n = 397). Blood pressure-related single-nucleotide polymorphisms (SNPs) were screened using genome-wide association analyses (p < 1 × 10^-5), and selected variants were used to construct weighted GRSs. Models integrating GRSs with body mass index (BMI), brachial-ankle pulse wave velocity (ba-PWV), and urinary 8-epi-prostaglandin F_2α (8-epi-PGF_2α) were evaluated by multivariable logistic regression and receiver operating characteristic analysis, with 1000-bootstrap internal validation. Three SNPs formed the total-sample GRS (rs13175330, rs117559502, rs62099117; adjusted odds ratio [OR] = 3.20) and three formed the female GRS (rs13175330, rs6001482, rs62099117; adjusted OR = 2.80); no stable male-specific GRS met prespecified criteria. The final discrimination models achieved an area under the curve of 0.833 in the total sample and 0.913 in females (BMI + ba-PWV + 8-epi-PGF_2α + GRS), and 0.758 in males (BMI + ba-PWV + 8-epi-PGF_2α). These findings support sex-aware hypertension risk characterization and warrant external and prospective validation.