Assessing the predictive efficacy of European-based systolic blood pressure polygenic risk scores in diverse Brazilian cohorts

Abstract

Abstract Despite the identification of numerous genetic variants affecting SBP in European populations, their applicability in admixed populations remains unclear. This study evaluates the predictive efficacy of a systolic blood pressure (SBP) polygenic risk score (PRS), derived from the UK Biobank data, in two Brazilian cohorts. We analyzed 944 K genetic variants consistent across an independent UK Biobank dataset, Brazilian cohorts, and HapMap database. Results show a significant association between increased PRS and SBP, as well as hypertension, in each study groups analyzed. An increase of one standard deviation in the PRS showed a significant association with SBP (β [95% CI] (mmHg) = 5.2 [5.1–5.3], 2.8 [2.1–3.5] and 2.6 [2.2–3.0]) and hypertension (odds ratio (OR) [95% CI] = 1.56 [1.54–1.56], 1.28 [1.2–1.4] and 1.47 [1.3–1.6]) in an independent UKB dataset, Baependi, and Pelotas, respectively. The associations were weaker in the Brazilian samples and the reduced association was noticeable in the Pelotas vs. the UK comparison for hypertension stages 1 and 2 (OR [95% CI] = 2.1 [1.5–3.1] and 3.0 [1.9–4.7] vs. 2.5 [2.2–2.8] and 4.9 [4.4–5.6]), whereas the Baependi data showed no significance for stage 1 hypertension. This trend mirrors findings in homogeneous African and Asian populations with diverse genetic architecture, highlighting the limitations of European-based PRS also in admixed populations. These insights are crucial for developing tailored disease prevention and management strategies in ethnically diverse groups.