# Dissecting the spectrum of genetic architectures underlying congenital heart defects.

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $156,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Individualized risk assessment, diagnosis, and treatment based on the integration of genomic data with clinical
data represent the promise of precision medicine. Despite the successes of clinical exome sequencing in rare
disease, more than half of all cases remain undiagnosed. The variants that are called in these clinical studies
are typically protein-coding variants, where it is easier to predict what the effect of a genetic variant is on
protein function. Previous studies of structural defects have identified non-coding variants have been
associated with specific gene regulatory domains in preaxial polydactyly and Pierre Robins’ Sequence, both
isolated structural defects affecting limb and craniofacial development, respectively. Therefore, we hypothesize
that there are other rare non-coding variants that can result in cardiac malformations. This proposal is focused
towards the untested 99% of the genome: the non-coding genome. Non-coding variants regulates the timing
and cell-specific expression of protein-coding genes. Our goal is to determine the roles of non-coding variants
in congenital heart disease (CHD), focusing on both rare non-coding genetic variation (Aim1) and integration
of common genetic variation using polygenic risk scores (Aim 2). The unique data sets available through the
Gabriella Miller Kids First Data Resource have whole-genome sequencing data for 298 patients affected with
CHD and 1 or more parents. This data set allows for novel exploration of the hypothesis that non-coding
variants drive the penetrance and expressivity in CHD. Findings from our study will advance our ability to
interpret how the non-coding genome can affect risk of congenital heart disease. Furthermore, we will advance
precision medicine approaches with respect to integrating non-coding genomic information into clinical
diagnostics.

## Key facts

- **NIH application ID:** 10077356
- **Project number:** 5R03HL150604-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Valerie A Arboleda
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $156,000
- **Award type:** 5
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077356

## Citation

> US National Institutes of Health, RePORTER application 10077356, Dissecting the spectrum of genetic architectures underlying congenital heart defects. (5R03HL150604-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10077356. Licensed CC0.

---

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