# Targeted Sequencing Study of GWAS-implicated Blood Pressure Loci

> **NIH NIH P20** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $259,613

## Abstract

Project Summary (Research Project 1)
 The overall objective of the proposed study is to identify novel genes and functional genetic variants
associated with blood pressure (BP) at 9 loci which attained genome-wide significance in the recent Asian
Genetic Epidemiology Network (AGEN)-BP genome-wide association study (GWAS) meta-analysis using next
generation sequencing technology. The proposed study will be carried out among 5,000 Han Chinese
participants of the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA). InterASIA
provides an extraordinary resource on BP-related phenotypes as well as sufficient quantities of DNA already
stored at our laboratories for genetic research. In the proposed study, we will discover novel functional variants
by deep sequencing contiguous genomic regions of 9 GWAS-implicated loci among 300 InterASIA participants
with the highest mean arterial pressure (MAP) and 300 participants not taking antihypertension medication with
the lowest MAP. This agnostic sequencing approach will allow us to examine intergenic variants with
potentially important but not well-understood regulatory functions as well as all 15 known genes at these loci,
which span an average of 155 kilobases each. Bioinformatic tools will be used to filter the large number of
discovered variants, prioritizing those with predicted functional relevance. To maximize statistical power, rare
variants will be grouped using: 1) an agnostic sliding window approach which aggregates rare variants in
adjacent and overlapping segments across the entire loci; and 2) a biology-based approach which aggregates
rare variants by known functional units (e.g. conserved region or gene). We will use state-of-the-art statistical
methods to examine the collective effects of rare variants in aggregate analyses. Novel low-frequency and
common variants will be examined separately using traditional single-marker analyses. We will genotype the
200 most promising novel variants among the remaining 4,400 InterASIA participants and test the association
between each variant and BP among the 5,000 (4,400 genotyped + 600 sequenced) InterASIA participants.
We will replicate each of the 25 most promising variants in an independent random sample of 10,000 Han
Chinese participants. In addition, we will leverage existing GWAS, whole-exome, and phenotype data available
in the database of Genotypes and Phenotypes to assess the trans-ethnic relevance of the 25 most promising
BP variants within large, population-based samples of up to 15,076 African-American and 30,821 European-
American participants. Ancestry-specific and overall meta-analyses will then be carried out. These findings
may have important clinical and public health implications. By helping to elucidate the biological pathways
underlying BP regulation, these findings may be used to develop novel gene-based strategies for the
prevention and treatment of hypertension. Furthermore, the experience gained by the ...

## Key facts

- **NIH application ID:** 9930643
- **Project number:** 5P20GM109036-05
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Tanika Nicole Kelly
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $259,613
- **Award type:** 5
- **Project period:** — → 2022-07-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930643

## Citation

> US National Institutes of Health, RePORTER application 9930643, Targeted Sequencing Study of GWAS-implicated Blood Pressure Loci (5P20GM109036-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9930643. Licensed CC0.

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