# Using genetics to discover mechanisms of myocardial infarction

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $721,541

## Abstract

Project Summary
The goal of this R01 proposal is to uncover biological mechanisms underlying association at known CAD and
MI loci to provide insight into treatment and prevention of cardiovascular disease. Our research team
combines strengths in cardiovascular disease, 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.
Building on our previous work where we identified genomic regions associated with CAD and MI, we propose
to uncover the mechanisms underlying association at CAD and MI loci using genetics and epigenomics. In the
previous funding period, we performed whole genome sequencing of 2,202 early-onset MI cases and healthy
controls. We also newly genotyped ~100,000 samples with a GWAS array with enrichment for coding variants.
In Aim 1, we propose to assess the phenotypic impact of the ~19 million variants and 20k indels and SVs
identified from HUNT sequenced samples by imputing them into 100,000 new GWAS samples with many
cardiovascular phenotypes. We will perform integrated analyses with epigenomics data to highlight clusters of
loci with related function. In Aim 2, we will perform targeted sequencing of 200 genes in 13,400 multi-ethnic MI
and CAD cases and controls to search for high effect genetic variants that implicate CAD genes. In Aim 3, we
will experimentally determine the functional variants and the mechanisms of action at 6-8 loci by introducing
genetic changes into cell lines, iPS cells or animal models.
Completion of these aims 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:** 10460334
- **Project number:** 5R01HL109946-09
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** YUQING Eugene CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $721,541
- **Award type:** 5
- **Project period:** 2011-08-18 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460334

## Citation

> US National Institutes of Health, RePORTER application 10460334, Using genetics to discover mechanisms of myocardial infarction (5R01HL109946-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10460334. Licensed CC0.

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