# Relations of Mitochondrial Genetic Variation and Function with Atrial Fibrillation

> **NIH NIH K01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $151,619

## Abstract

Project Abstract
The proposed study brings together the applicant's training in mitochondrial physiology and cardiovascular
diseases with additional training in bioinformatics, biostatistics, and genetic epidemiology. To this end, a
multidisciplinary team of investigators has been assembled to aid the applicant in her training and studies.
Further, participation in the programs offered by the Boston University School of Medicine's Faculty
Development and Diversity office under the directorship of one of the applicant's primary co-mentors will help
her in her professional development and in transitioning to independence. The mechanisms underlying the
association of advancing age with atrial fibrillation (AF) are unclear. Declines in mitochondrial function have
long been appreciated to play a role in aging but whether alterations in mitochondrial genetics and function
underlie age-related AF has not been thoroughly evaluated. The greater sensitivity afforded by whole genome
sequencing provides novel opportunities to evaluate specific alterations in mtDNA and AF. We hypothesize
that the accumulation of mitochondrial DNA (mtDNA) mutations with advancing age corresponds with a
decline in mitochondrial function that promotes the development of AF. For Aim 1, the applicant will describe
the mitochondrial genetic diversity within a multiethnic population of >65,000 participants within the NHLBI's
Trans-Omics for Precision Medicine (TOPMed) using bioinformatics annotations and functional predictions of
mtDNA mutations (PolyPhen-2, PredictSNP, MFold). We will assess the relations of mtDNA mutations and
copy number with advancing age and AF in TOPMed (Aim 2). In Aim 3, oxidative phosphorylation complex
activities will be measured in TOPMed biobanked samples from sex- and comorbidity-matched participants
with and without the variants associated with AF from Aim 2 (N=150/group), using immunocapture,
spectrophotometric assays. A greater understanding of the contribution of mtDNA mutations in AF will provide
insights that could be utilized in precision medicine to identify individuals for specific pharmaceutical targets
and lifestyle changes aimed at altering mitochondrial metabolism and downstream signaling processes. The
additional training and protected time afforded by the K01 will aid the applicant in making her transition to an
independent investigator studying the intersections of mtDNA, mitochondrial physiology, and cardiovascular
disease.

## Key facts

- **NIH application ID:** 10176176
- **Project number:** 5K01HL143142-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Jessica L Fetterman
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $151,619
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176176

## Citation

> US National Institutes of Health, RePORTER application 10176176, Relations of Mitochondrial Genetic Variation and Function with Atrial Fibrillation (5K01HL143142-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10176176. Licensed CC0.

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