| Title: | Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality |
| Journal: | Nature Communications |
| Published: | 30 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37777527/ |
| DOI: | https://doi.org/10.1038/s41467-023-41785-7 |
| URL: | https://www.nature.com/articles/s41467-023-41785-7.pdf |
Publication 9443
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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.</p>
26 Authors
- Yun Soo Hong
- Stephanie L. Battle
- Wen Shi
- Daniela Puiu
- Vamsee Pillalamarri
- Jiaqi Xie
- Nathan Pankratz
- Nicole J. Lake
- Monkol Lek
- Jerome I. Rotter
- Stephen S. Rich
- Charles Kooperberg
- Alex P. Reiner
- Paul L. Auer
- Nancy Heard-Costa
- Chunyu Liu
- Meng Lai
- Joanne M. Murabito
- Daniel Levy
- Megan L. Grove
- Alvaro Alonso
- Richard Gibbs
- Shannon Dugan-Perez
- Lukasz P. Gondek
- Eliseo Guallar
- Dan E. Arking
1 Application
| Application ID | Title |
|---|---|
| 17731 | A phenome-wide association study of copy number variation |
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