Faculty, Staff and Student Publications
Publication Date
9-30-2023
Journal
Nature Communications
Abstract
Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia.
Keywords
Humans, Mitochondria, DNA, Mitochondrial, Heteroplasmy, Leukemia, Mutation, Genetic markers, Genetics research
DOI
10.1038/s41467-023-41785-7
PMID
37777527
PMCID
PMC10542802
PubMedCentral® Posted Date
September 2023
PubMedCentral® Full Text Version
Post-print