Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Probing Phenotype-Genotype Relations After Whole Genome Sequencing in Patients with Atrial Fibrillation

Award Number: R01HL155197
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

Group Awards By:

View Award Description

Probing Phenotype-Genotype Relations After Whole Genome Sequencing in Patients with Atrial Fibrillation - Most cases of atrial fibrillation (AF) arise from a combination of clinical risk factors and genetic susceptibility. Moreover, it has recently become clear that AF can be the earliest manifestation of rare high effect size variants associated with potentially fatal cardiac channelopathies or cardiomyopathies (CM). When inherited arrhythmia/CM syndromes are suspected, current guidelines recommend genetic testing to enable early detection and reduce the risk of sudden cardiac death. However, current guidelines specifically state that genetic testing should not ordinarily be performed in patients presenting with AF alone. Thus, major knowledge gaps are how to identify those patients in whom AF is the first sign that they possess a potentially serious underlying genetic disease and what is the cardiac phenotype and clinical significance of those rare genetic variants. We are now in a position to address these issues using the NHLBI’s Trans-omics for Precision Medicine (TOPMed) and NHGRI’s Centers for Common Disease Genomics (CCDG) resources. TOPMed has performed whole genome sequencing (WGS) and CCDG has performed whole exome sequencing (WES) in large numbers of subjects with common cardiovascular diseases. Currently, this includes 2,852 participants with early onset AF (age <60 years, a group in which genetic factors may play an especially important role) from Vanderbilt (Vanderbilt TOPMed AF Cohort=1,161, Vanderbilt CCDG AF Cohort=1,691). These participants were recruited from Vanderbilt AF registries and have consented for potential recontact. Using these resources, Aim 1 will perform deep phenotyping to define the cardiac phenotype of AF patients with a pathogenic or likely pathogenic (P/LP) rare variant associated with an inherited cardiomyopathy (CM) syndrome (e.g. arrhythmogenic CM, hypertrophic CM, dilated CM; Aim 1A) or inherited arrhythmia syndrome (e.g. Brugada Syndrome, Long QT Syndrome; Aim 1B) and compared to controls. Participants from these defined genetic subgroups and controls will be recruited for an outpatient research visit to undergo a cardiac MRI, rest/stress/signal-averaged ECGs, and cardiac monitoring. If an inherited arrhythmia/CM syndrome is diagnosed, guideline-directed changes to medical care will be recommended. Aim 2 will create a prediction tool using clinical risk factors ± an AF polygenic risk score to identify patients with AF who have a P/LP rare genetic variant and therefore should undergo genetic testing. While advances in sequencing technology have improved the understanding of how rare and common genetic variation contributes to AF susceptibility, the phenotype of AF genetic subgroups remains incompletely defined. If genetic testing for AF is to add therapeutic value, our work to identify who should be tested and define the clinical implications of these results in a broad AF population is needed.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $683,303 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cardiovascular Diseases Research	001	5	9/5/2025	NON-COMPETING CONTINUATION	$683,303
2025	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cardiovascular Diseases Research	000	4	6/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $683,303

Issue Date FY: 2024 ( Subtotal = $819,070 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cardiovascular Diseases Research	000	4	8/9/2024	NON-COMPETING CONTINUATION	$819,070
														Subtotal = $819,070

Issue Date FY: 2023 ( Subtotal = $835,785 )
2023	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cardiovascular Diseases Research	000	3	8/4/2023	NON-COMPETING CONTINUATION	$835,785
														Subtotal = $835,785

Issue Date FY: 2022 ( Subtotal = $856,293 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cardiovascular Diseases Research	000	2	8/18/2022	NON-COMPETING CONTINUATION	$856,293
														Subtotal = $856,293

Issue Date FY: 2021 ( Subtotal = $863,694 )
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Cardiovascular Diseases Research	000	1	9/1/2021	NEW	$863,694
														Subtotal = $863,694

Grand Total All Awards = $4,058,145

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Probing Phenotype-Genotype Relations After Whole Genome Sequencing in Patients with Atrial Fibrillation

Award Number: R01HL155197

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer