# Analysis of Heteroplasmic mtDNA Mutations in Whole Genome Sequencing: Methods and Application to Cardiometabolic Disease Traits

> **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $122,450

## Abstract

PROJECT SUMMARY
Mitochondrial DNA (mtDNA) sequence variations have been causally implicated in cardiometabolic diseases
(CMDs). However, the mechanisms linking mtDNA mutations to CMDs are not fully elucidated. Each human cell
contains as many as 10,000 copies of mtDNA. As a result, there are two types of mtDNA mutations –
homoplasmic and heteroplasmic mutations. The latter represent the coexistence of two (or more) mtDNA alleles
in the same cell or across cells. For most heteroplasmic mtDNA mutations, the proportion of mutant alleles is
low and can only be detected by deep sequencing of mtDNA. Whole genome sequencing (WGS) through
NHLBI’s Trans-Omics for Precision Medicine program has generated deep WGS data, including mtDNA, in tens
of thousands of individuals, offering an unprecedented opportunity to investigate heteroplasmic mtDNA
mutations in relation to CMDs. We propose to develop rigorous methods and a software suite to facilitate
association studies of heteroplasmic mtDNA mutations in large samples. The novel methods and the software
suite will be open source and available to the broad scientific community to study mtDNA sequence variation
with respect to age-related diseases, including CMDs. The body of knowledge generated by these future findings
will facilitate the development of new modalities for the diagnosis, prevention, and treatment of age-related
diseases.

## Key facts

- **NIH application ID:** 9859469
- **Project number:** 5R21HL144877-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Chunyu Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,450
- **Award type:** 5
- **Project period:** 2019-02-04 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859469

## Citation

> US National Institutes of Health, RePORTER application 9859469, Analysis of Heteroplasmic mtDNA Mutations in Whole Genome Sequencing: Methods and Application to Cardiometabolic Disease Traits (5R21HL144877-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9859469. Licensed CC0.

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