ArticleFrontiers in cardiovascular medicine2026
Pathway-specific polygenic risk scores for blood pressure traits in a West African cohort.
Article in Frontiers in cardiovascular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Genome-wide polygenic risk scores (PRSs) are useful for stratifying individuals' risk of polygenic diseases such as hypertension. However, a limitation of genome-wide PRSs is that they do not provide information about the distribution of risk burden across biological pathways. We used pathway-specific PRSs to investigate these effects of common antihypertensive therapy target pathways on disease risk in a cohort of West African individuals. Methods: A total of 11 pathways, comprising 1,149 unique genes, were selected based on the targets of commonly used antihypertensive agents. Pathway-specific PRSs for hypertension [individuals with systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg, or taking antihypertensive medications] were calculated in a cohort of 2,295 individuals. The model was then validated and tested in independent cohorts of 1,614 and 966 individuals, respectively. All participants were recruited from the International Collaborative Study on Hypertension in Blacks. Results: In the combined pathway analysis, PRSs predicted risk better than base models fitted only with sex, age, and principal components. Compared with the base models without the PRSs, incremental increases in Conclusions: Combined pathway polygenic risk scores derived from genes in well-defined genetic pathways predict hypertension risk in individuals of African ancestry. However, the relatively low predictability of pathway-specific PRSs supports the need to explore the broader influence of genetic, environmental, and epigenetic factors that cannot be captured by pathway-specific PRSs alone.
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