# Using GenTAC Resources in BioLINCC to discover BAV-specific Aortic Phenotypes

> **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $123,750

## Abstract

Program Director/Principal Investigator (Last, First, Middle):
PROJECT SUMMARY / ABSTRACT
Bicuspid aortic valve (BAV) is the most frequent congenital valvular cardiac malformation, occurring in 0.5-
1.2% of the US population. Over 20% of patients with BAV develop thoracic aortic aneurysm or dissection
(TAAD) requiring surgery. Yet, untreated TAAD is associated with high morbidity and mortality rates dying of
aortic rupture, cardiac tamponade, acute aortic insufficiency and organ ischemia. TAAD is relatively rare in the
general population, but is more frequent in individuals with BAV, often requiring surgery at a much younger age
than the general population.
Yet, we know little of the genetic etiology, cellular biology and modifiers of disease progression for BAV to
TAAD, including heterogeneity of BAV leaflet fusion morphology that has impact upon blood flow patterns in
the aortic root and ascending aorta.
Common variants in the fibrillin-1 (FBN1) gene in non-familial aortic aneurysm in patients have been observed
in patients with and without BAV. Using genome-wide association, we have observed modest signals from
common non-coding variants in FBN1 and other genes, with aortic dimensions in BAV patients. The etiology
and presentation of TAAD is most likely due to a full spectrum of frequent to private mutations that can only be
fully explored with GWAS of a sufficiently-powered cohort of well-phenotyped patients. These mutations may
have overlap with TAAD-associated mutations in patients with a tricuspid aortic valve.
In order to expeditiously advance the field of BAV TAAD research, with adequate sample size for genetic
studies that include a wide range of BAV phenotypes, we plan to use the pre-exisiting DNA, epidemiologic and
well-imaged phenotypes of patients with BAV, from the National Registry of Genetically Triggered Thoracic
Aortic Aneurysms and Cardiovascular Conditions (GenTAC) housed in BioLINCC. To increase power of the
study, we will use additional BAV patients, along with comparable control patients from other cohorts including
the BAV Consortium (BAVCon), the Michigan Cardiovascular Health Improvement Project (CHIP) and BAV
Registry, and the University of Texas, Houston.
This proposal provides a credible and best mechanism for identifying rare, as well as common genetic variation
causing TAAD in individuals with BAV, notably by inclusion of the GenTAC resources housed at BIOLINCC, in
concert with the extensive resources of other supplemental studies. We believe these methods will allow for
critical advances in BAV research and potentially, patient management.
OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10103878
- **Project number:** 7R21HL150373-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Simon C Body
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $123,750
- **Award type:** 7
- **Project period:** 2019-09-17 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10103878

## Citation

> US National Institutes of Health, RePORTER application 10103878, Using GenTAC Resources in BioLINCC to discover BAV-specific Aortic Phenotypes (7R21HL150373-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10103878. Licensed CC0.

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