A multi-ethnic polygenic risk score for chronic kidney disease is associated with increased risk of hypertension in African American individuals

Background Hypertension (HT) and chronic kidney diseases (CKD) are complex conditions having both genetic and environmental contributions, disproportionately affecting African American (AA) individuals. Recent evidence is contradictory regarding the directionality of the relationship between the two...

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Published in:BMC nephrology Vol. 26; no. 1; pp. 524 - 11
Main Authors: Kakar, Aastha, Litkowski, Elizabeth M., Scadden, Ashley W., Anwar, Mohammad Y., Konigsberg, Iain R., Stanislawski, Maggie A., DuPre, Natalie C., Mitra, Riten, Baumgartner, Richard, Raffield, Laura M., Lange, Ethan M., Lange, Leslie A., Taylor, Kira C.
Format: Journal Article
Language:English
Published: London BioMed Central 26.09.2025
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects:
African american individuals
African Americans
Antihypertensives
Blood pressure
Chronic kidney disease
Chronic kidney failure
Complications and side effects
Ethnicity
Genetic aspects
Genomes
Health aspects
Health risk assessment
Hypertension
Internal Medicine
Kidney diseases
Medical research
Medicine
Medicine & Public Health
Medicine, Experimental
Nephrology
Physiological aspects
Polygenic inheritance
Polygenic risk scores
Premature mortality
Regression analysis
Risk factors
Urine
United States
Polygenic risk scores
Hypertension
Chronic kidney disease
African american individuals
ISSN:1471-2369, 1471-2369
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Summary:Background Hypertension (HT) and chronic kidney diseases (CKD) are complex conditions having both genetic and environmental contributions, disproportionately affecting African American (AA) individuals. Recent evidence is contradictory regarding the directionality of the relationship between the two conditions. This study investigates the relationship between CKD and blood pressure (BP)-related traits with CKD and BP by generating polygenic risk scores (PRSs) for CKD and BP-related traits in 2,995 participants of the Jackson Heart Study, a prospective cohort study of AA individuals from the Jackson, Mississippi metropolitan area. Methods We used multivariable regression models to evaluate associations of each PRS with CKD, HT, systolic blood pressure (SBP) and diastolic blood pressure (DBP), adjusting for age, sex, and genetic ancestry. Results We observed positive associations for the CKD PRS (CKD-PRS) with both CKD (OR per standard deviation increase, 95% CI: 1.85, 1.64–2.09) and HT (1.10, 1.01–1.20). Adding the CKD-PRS to a multivariable model for CKD increased the area under the receiver operating curve (AUC) by 0.061. The CKD-PRS was also positively associated with DBP (beta = 0.37 mmHg, 95% CI: 0.01–0.73). The BP-PRSs were positively associated with HT, SBP and DBP; however, they were not associated with CKD. Conclusions Our results suggest that genetic predisposition to CKD may increase the risk of hypertension in AA individuals. Our results also align with previous studies in European ancestry individuals that fail to support the causative role of blood pressure in kidney function decline, as we did not find an association between the blood pressure risk scores with CKD. Finally, we found a strong association between the CKD risk score with CKD in AA individuals, supporting its clinical use in an AA population. Overall, our findings provide valuable insights into the genetic underpinnings of CKD and HT in AA individuals.
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ISSN:1471-2369
1471-2369
DOI:10.1186/s12882-025-04425-4