# Investigating the contribution of rare coding variants to cardiovascular diseases

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2020 · $38,810

## Abstract

Project Summary
Cardiovascular diseases are one of the leading causes of death in the United States. Large genome-wide
association studies have been able to detect links between cardiovascular phenotypes and a number of
regions in the genome. However, given the sample sizes available in the majority of studies and the effect
sizes on these phenotypes, the associations are limited to common variants (minor allele frequency >1%).
Furthermore, these studies can only implicate regions of the genome without identifying what the causal
variants may be. I propose to develop a pipeline to better understand the contribution of rare variants to
cardiovascular disease architectures. First, I will use a much larger dataset than previously available to
determine associations between rare variants and cardiovascular traits. I will then filter this list using additional
information about linkage disequilibrium and variant impact to create a short-list of putatively causal, high-
impact, rare coding variants. Second, using the same large dataset, I will create collapsed by gene genotypes
of whether individuals carry ultrarare coding and loss-of-function variants. This will allow me to detect
associations between phenotypes and genes that were not detected through traditional association tests by
examining the contribution of ultrarare variants. Finally, I will investigate the relationship between variants that
modify gene expression and the effects of rare coding variants. In the case where individuals carry one copy of
a rare loss-of-function mutation, an increased amount of wildtype protein produced from their other haplotype
might be able to mitigate their expected phenotype. By examining, whether this appears to be the case, I will
better be able to predict the variable penetrance of rare coding variants that contribute to some cardiovascular
traits. Characterizing the role of rare coding variants in cardiovascular diseases will enhance our understanding
of the genetic architecture of these traits and the genes and pathways involved.

## Key facts

- **NIH application ID:** 10062042
- **Project number:** 1F31HL154537-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Alison Rachel Barton
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,810
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062042

## Citation

> US National Institutes of Health, RePORTER application 10062042, Investigating the contribution of rare coding variants to cardiovascular diseases (1F31HL154537-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10062042. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*