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[Preprint]. 2025 Jun 24:rs.3.rs-6674221.
doi: 10.21203/rs.3.rs-6674221/v1.

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

Aastha Kakar  1 , Elizabeth M Litkowski  2 , Ashley W Scadden  2 , Mohammad Y Anwar  3 , Iain R Konigsberg  2 , Maggie A Stanislawski  2 , Natalie C DuPre  1 , Riten Mitra  1 , Richard Baumgartner  1 , Laura M Rsffield  3 , Ethan M Lange  2 , Leslie A Lange  2 , Kira C Taylor  1
Affiliations

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

Aastha Kakar et al. Res Sq. .

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 AA participants of the Jackson Heart Study.

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 (ROC) curve 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 indicate 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: African American individuals; Chronic kidney disease; Hypertension; Polygenic risk scores.

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Figures

Figure 1
Figure 1
CKD-PRS Deciles. Top (A,B): OR for chronic kidney disease (CKD) and hypertension (HT) status by deciles of CKD-PRS in JHS. Error bars indicate confidence intervals of the odds ratio; reference decile was set to decile 1. Bottom (C,D): Relationship between mean SBP and mean DBP with deciles of CKD-PRS in JHS. Error bars indicate standard error of the mean.
Figure 2
Figure 2
SBP-PRS deciles. Top (A,B): OR for chronic kidney disease (CKD) and hypertension (HT) status by deciles of SBP-PRS in JHS. Error bars indicate confidence intervals of the odds ratio; reference decile was set to decile 1. Bottom (C,D): Relationship between mean SBP and mean DBP with deciles of SBP-PRS in JHS. Error bars indicate standard error of the mean.
Figure 3
Figure 3
DBP-PRS deciles. Top (A,B): OR for chronic kidney disease (CKD) and hypertension (HT) status by deciles of DBP-PRS in JHS. Error bars indicate confidence intervals of the odds ratio; reference decile was set to decile 1. Bottom (C,D): Relationship between mean SBP and mean DBP with deciles of DBP-PRS in JHS. Error bars indicate standard error of the mean.
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