# Cardiorenal Genomics for Risk Prediction in African Descent Populations

> **NIH NIH R35** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $859,443

## Abstract

ABSTRACT
Hypertension (HTN) and chronic kidney disease (CKD) overburden African Americans (AAs). These disparities
translate to higher rates of cardiorenal disease endpoints including stroke, coronary heart disease (CHD), end
stage renal disease (ESRD), and death. Blood pressure (BP) lowering with antihypertensive treatment reduces
the risk of these outcomes, but the effects of treatment may be variable in different race groups. Studies have
demonstrated that AAs respond best to calcium channel blockers and diuretics and not as well to to beta-
blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers in comparison to their
European American (EA) counterparts. The reasons for differences in cardiorenal health and antihypertensive
treatment response are multifactorial and thought to include both environmental and inherited factors. Prior
genetic and pharmacogenetic association studies of HTN and BP response to antihypertensive agents have
been undertaken in AAs, but these studies have been considerably smaller in scope and sample size compared
to those of EA populations. Smaller samples sizes of existing genetic datasets have hindered polygenic risk
prediction in this population with the potential to create new health disparities. In order to overcome the limitations
of previous research and enable efforts in personalized medicine in AAs, we will leverage data from existing
cohorts for one of the largest genomic and pharmacogenomic studies of cardiorenal traits to date. Our
pharmacogenetic discovery includes >4000 AAs randomized to chlorthalidone and >2500 randomized to
lisinopril from the GenHAT study, an ancillary study of the Antihypertensive and Lipid Lowering Treatment to
Prevent Heart Attack Trial. We have established an agreement with the International Consortium for
Antihypertensives Pharmacogenomics Studies (ICAPS) for validation of our findings. Our genomic discovery is
anchored in whole-genome imputed GWAS data from ~12000 REGARDS study AA participants and ~5000 AAs
(JHS, Genoa, HyperGEN) with relevant phenotype and genotype data from the NHLBI’s Trans-Omics for
Precision Medicine (TOPMed) program. We will replicate our top variant-association findings in additional
populations (~11,000 AAs) with relevant data followed by polygenic risk score testing in other cohorts from
TOPMed. Using these rich resources we will derive new screening tools for antihypertensive treatment response
and cardiorenal diseases. Polygenic risk score applications are increasing in other populations and this research
will substantially improve the available data in underrepresented AAs. .

## Key facts

- **NIH application ID:** 10107584
- **Project number:** 1R35HL155466-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Marguerite R Irvin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $859,443
- **Award type:** 1
- **Project period:** 2021-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107584

## Citation

> US National Institutes of Health, RePORTER application 10107584, Cardiorenal Genomics for Risk Prediction in African Descent Populations (1R35HL155466-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10107584. Licensed CC0.

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