# Genetics of CKD and Hypertension-Risk Prediction and Drug Response in the MVP

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Genetics of CKD and Hypertension—Risk Prediction and Drug Response in the MVP
Chronic kidney disease (CKD) affects 850 million people worldwide. Preventing the development
of CKD and slowing its progression is critical to reducing premature death and end-stage renal
disease (ESRD) in this growing population. Risk prediction and early treatment of people at risk
for or with CKD is of upmost relevance to reduce the complications of kidney disease. First, we
will generate weighted Genetic Risk Scores (GRS) for the prediction of incident and
progressive CKD, and test if we can improve prediction beyond common clinical risk factors. Our
primary approach to generating GRSes will include loci from the glomerular filtration rate (GFR)
trait genome wide association scan (GWAS) (270 participants,156 SNPs), and Blood pressure
(BP) trait GWAS (781,119 participants, 498 SNPs) that reached genome wide significance,
allowing us to evaluate the shared genetic contribution of these traits to CKD severity. The genetic
information we will include in the GRS is far more extensive than previously included in CKD
studies, and should improve risk prediction when added to incident and progressive CKD risk
equations. As a secondary approach, we will generate and test polygenic risk scores (PRS)
to evaluate the benefit of including even a larger set of variants (not limited to the ones that reach
GWAS significance) in risk prediction. 2) Second, we will extend our work in resistant
hypertension (RH), a potent risk factor for the development of CKD and ESRD. In our RH GWAS
(17000 cases) 9 we identified three loci with either predicted gene expression10 in the adrenal
gland [relaxin (RXFP2), fibrillin-2 (FBN2)] or located in a gene (CACNA1D) whose mutations have
been recognized in aldosterone producing adenomas11,12. It has been recently acknowledged
that there is a broad spectrum of manifestations of subclinical primary hyperaldosteronism,
whose prevalence is much greater than previously recognized13, and may precede future severe
hypertension (HTN) and incident CKD.4 13 We propose a series of pharmacogenomic studies to
identify the association between these variants and specific clinical drug response phenotypes
related to primary hyperaldosteronism (mild or subclinical forms), including thiazide-induced
hypokalemia14 with the goal of early detection and prevention of CKD. 3) Finally, mineral
metabolism disorders of CKD are important predictors of CKD progression and CV events. In this
aim, we will study the genetic determinants of mineral metabolism markers. This information will
help us to understand in the future the share genetic contribution of these traits to CKD. We will
accomplish our goals with the following specific aims: Aim 1a) To build a series of weighted
GRSes/PRS to summarize the genetic effects of markers derived from large GWA studies from
the MVP and test their ability to predict incident and progressive CKD. Aim 1b): To evaluate if the
addition of the ...

## Key facts

- **NIH application ID:** 9782808
- **Project number:** 1I01CX001897-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Adriana Hung
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2019-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9782808

## Citation

> US National Institutes of Health, RePORTER application 9782808, Genetics of CKD and Hypertension-Risk Prediction and Drug Response in the MVP (1I01CX001897-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9782808. Licensed CC0.

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