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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| Veröffentlicht in: | BMC nephrology Jg. 26; H. 1; S. 524 - 11 |
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| Sprache: | Englisch |
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BioMed Central
26.09.2025
BioMed Central Ltd Springer Nature B.V BMC |
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| Abstract | 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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| AbstractList | 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. Keywords: Polygenic risk scores, Chronic kidney disease, Hypertension, African american individuals Abstract 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. 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. 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. 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. 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. 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. Section BackgroundHypertension (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.AbstractSection MethodsWe 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.AbstractSection ResultsWe 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.AbstractSection ConclusionsOur 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. |
| ArticleNumber | 524 |
| Audience | Academic |
| Author | Scadden, Ashley W. Baumgartner, Richard Lange, Ethan M. Taylor, Kira C. Stanislawski, Maggie A. DuPre, Natalie C. Lange, Leslie A. Anwar, Mohammad Y. Konigsberg, Iain R. Raffield, Laura M. Mitra, Riten Kakar, Aastha Litkowski, Elizabeth M. |
| Author_xml | – sequence: 1 givenname: Aastha surname: Kakar fullname: Kakar, Aastha email: aastha.kakar@cuanschutz.edu organization: Department of Epidemiology & Population Health, School of Public Health & Information Sciences, University of Louisville, Department of Biomedical Informatics, School of Medicine, University of Colorado Anschutz Medical Campus – sequence: 2 givenname: Elizabeth M. surname: Litkowski fullname: Litkowski, Elizabeth M. organization: Department of Biomedical Informatics, School of Medicine, University of Colorado Anschutz Medical Campus – sequence: 3 givenname: Ashley W. surname: Scadden fullname: Scadden, Ashley W. organization: Department of Biomedical Informatics, School of Medicine, University of Colorado Anschutz Medical Campus – sequence: 4 givenname: Mohammad Y. surname: Anwar fullname: Anwar, Mohammad Y. organization: Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill – sequence: 5 givenname: Iain R. surname: Konigsberg fullname: Konigsberg, Iain R. organization: Department of Biomedical Informatics, School of Medicine, University of Colorado Anschutz Medical Campus – sequence: 6 givenname: Maggie A. surname: Stanislawski fullname: Stanislawski, Maggie A. organization: Department of Biomedical Informatics, School of Medicine, University of Colorado Anschutz Medical Campus – sequence: 7 givenname: Natalie C. surname: DuPre fullname: DuPre, Natalie C. organization: Department of Epidemiology & Population Health, School of Public Health & Information Sciences, University of Louisville – sequence: 8 givenname: Riten surname: Mitra fullname: Mitra, Riten organization: Department of Epidemiology & Population Health, School of Public Health & Information Sciences, University of Louisville – sequence: 9 givenname: Richard surname: Baumgartner fullname: Baumgartner, Richard organization: Department of Epidemiology & Population Health, School of Public Health & Information Sciences, University of Louisville – sequence: 10 givenname: Laura M. surname: Raffield fullname: Raffield, Laura M. organization: Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill – sequence: 11 givenname: Ethan M. surname: Lange fullname: Lange, Ethan M. organization: Department of Biomedical Informatics, School of Medicine, University of Colorado Anschutz Medical Campus – sequence: 12 givenname: Leslie A. surname: Lange fullname: Lange, Leslie A. organization: Department of Biomedical Informatics, School of Medicine, University of Colorado Anschutz Medical Campus, Department of Epidemiology, School of Public Health, University of Colorado Anschutz Medical Campus – sequence: 13 givenname: Kira C. surname: Taylor fullname: Taylor, Kira C. organization: Department of Epidemiology & Population Health, School of Public Health & Information Sciences, University of Louisville |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/41013308$$D View this record in MEDLINE/PubMed |
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Hypertension (HT) and chronic kidney diseases (CKD) are complex conditions having both genetic and environmental contributions, disproportionately... Background Hypertension (HT) and chronic kidney diseases (CKD) are complex conditions having both genetic and environmental contributions, disproportionately... Hypertension (HT) and chronic kidney diseases (CKD) are complex conditions having both genetic and environmental contributions, disproportionately affecting... Section BackgroundHypertension (HT) and chronic kidney diseases (CKD) are complex conditions having both genetic and environmental contributions,... Abstract Background Hypertension (HT) and chronic kidney diseases (CKD) are complex conditions having both genetic and environmental contributions,... |
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| SubjectTerms | 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 |
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| Title | A multi-ethnic polygenic risk score for chronic kidney disease is associated with increased risk of hypertension in African American individuals |
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