# Genetic and Epigenetic Mechanisms of BP Regulation

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2024 · $2,309,802

## Abstract

OVERALL PROGRAM SUMMARY
One of the most significant challenges for understanding genetic control of blood pressure (BP) is that the vast
majority of BP-associated single nucleotide polymorphisms (SNPs) in humans are located in noncoding
regions of DNA. Many of these noncoding SNPs are located in haplotype regions thousands of base pairs
away from any protein-coding gene and their effects on BP cannot be explained by any currently known coding
or other functional sequence variant, making it nearly impossible to link these noncoding SNPs to genes or
physiological pathways that regulate BP based on genomic sequence. Understanding the effect of intergenic
noncoding SNPs on gene expression and the underlying mechanisms is a major challenge not just for BP and
hypertension research, but for research on nearly all complex traits and common diseases.
 The goal of this PPG proposal is to begin to address this major challenge and test the overall
hypothesis that noncoding SNPs associated with human BP but located far from any protein-coding
gene regulate gene expression in specific BP relevant cell types through epigenetic mechanisms and
these mechanisms can influence BP. We have developed three projects that each address one aspect of
this overall hypothesis. Project 1 will use precision genome editing to identify the effect of specific BP-
associated noncoding SNPs on gene expression in BP-relevant human cell types. Project 2 will test the
hypothesis that BP-associated noncoding SNPs influence the expression of BP-relevant genes through
epigenetic mechanisms including chromatin looping, enhancer function and noncoding RNA in human cells
and tissues. Project 3 will take this line of research to animal models in vivo to test directly the novel
hypothesis that chromatin conformation plays a role in BP regulation. The three projects will interact with, and
inform, each other extensively and, together, will achieve the overall goal of the program. All three projects will
rely on Core A for administrative support and Core B for sequencing coordination and data analysis.
 We have published at least 16 papers in the last few years that provide direct support for key aspects of
the conceptual validity and technical feasibility of this PPG. In addition, we have obtained a large amount of
preliminary data to further support the feasibility of the wide range of sophisticated and new technologies that
we will use and the validity of proposed novel hypotheses. This PPG represents a fundamentally new direction
for hypertension research. It will establish several novel approaches and technologies, generate unique and
extensive datasets, and provide new biological insights, all of which will help to advance genetic and epigenetic
research in hypertension and other disease areas.

## Key facts

- **NIH application ID:** 10903747
- **Project number:** 5P01HL149620-05
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** MINGYU LIANG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,309,802
- **Award type:** 5
- **Project period:** 2020-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903747

## Citation

> US National Institutes of Health, RePORTER application 10903747, Genetic and Epigenetic Mechanisms of BP Regulation (5P01HL149620-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10903747. Licensed CC0.

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