# The Identification and characterization of genetic variants underlying cardiovascular diseases

> **NIH NIH R35** · YALE UNIVERSITY · 2021 · $1,005,000

## Abstract

Cardiovascular disorders (CVD), including coronary artery disease (CAD) and
congenital hear diseases (CHD) are the leading causes of death in the United States.
Despite strong contribution of genetic factors to CVD, very little is known about the
underlying genetic causes of these diseases. We have embarked on high throughput
sequencing and high throughput in vivo characterization of genes underlying CVD in
outlier kindreds and in offsprings of consanguineous unions. Using whole-exome
sequencing (WES) and state of the art analytic approaches, from linkage to gene set
enrichment analysis, we have identified independent mutations that underlie CAD,
metabolic syndrome and diverse CHD. Our success in identification of disease genes is
in part due to access to unique disease populations across the world and the support of
Yale Center for Mendelian Genomics. While we have devised inventive approaches for
novel gene discovery, the distinctive feature of our laboratory is in pursuing the
characterization of disease genes in vivo and its success in identifying novel disease
pathways and targets for drug development. We have established high throughput
techniques in the lab for functional characterization of identified human mutations in vitro
and in vivo by employing novel gene editing techniques. Most recently, we have begun
to investigate the epigenetic effects of aging, diet and physical activity on disease
pathogenesis in human and animal models. Most notably, we have taken a step further
and have initiated collaborative efforts with the industry in order to screen and
characterize small molecules that can target identified disease pathways in order to
rescue cardiovascular and metabolic traits. Our highly cited published work is an attest
for the quality and the promising nature of the results we generate in the lab.

## Key facts

- **NIH application ID:** 10071188
- **Project number:** 5R35HL135767-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Arya Mani
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,005,000
- **Award type:** 5
- **Project period:** 2017-01-23 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071188

## Citation

> US National Institutes of Health, RePORTER application 10071188, The Identification and characterization of genetic variants underlying cardiovascular diseases (5R35HL135767-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10071188. Licensed CC0.

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