# Using Genetics to Inform Mechanism of Cardiovascular Disease

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $904,010

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this R35 proposal is to uncover novel genetic discoveries and biological mechanisms underlying
association with devastating cardiovascular diseases. This proposal builds on strengths in high-throughput
genetics and genomics and development and application of innovative computational and statistical methods
and genomics technology to maximize the benefits of genetic studies of cardiovascular disease.
We will continue our discovery efforts to uncover genetic variants associated with a variety of cardiovascular
diseases including atrial fibrillation, aortic aneurysm and dissection, and myocardial infarction and coronary
artery disease. Building on our previous work where we identified a number of new genes for coronary artery
disease and lipids, we also propose to uncover the mechanisms underlying association at known loci using
genetics and epigenomics. We propose to assess the phenotypic impact of the ~19 million variants and 20k
indels and SVs identified from whole genome sequenced samples by imputing them into 70,000 new GWAS
samples with many cardiovascular phenotypes. We will perform integrated analyses with epigenomics data to
highlight clusters of loci with related function. We also propose to perform targeted sequencing of 300 genes
in 30,000 CAD cases and controls to search for loss of function variants at CAD loci that implicate CAD genes.
We will continue to search for mechanistic insight by performing a PheWAS for all CAD-associated variants
identified, disentangling multiple independent signals and correlated traits and clinical endpoints using
conditional testing.
Completion of these studies will provide new insights into disease mechanisms that have the potential to
catalyze breakthroughs in cardiovascular disease prevention, treatment, and diagnosis.

## Key facts

- **NIH application ID:** 9856480
- **Project number:** 5R35HL135824-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Cristen J Willer
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $904,010
- **Award type:** 5
- **Project period:** 2017-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856480

## Citation

> US National Institutes of Health, RePORTER application 9856480, Using Genetics to Inform Mechanism of Cardiovascular Disease (5R35HL135824-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9856480. Licensed CC0.

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