ArticleNature communications2023
Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28citing papers in PubMed
5.1field-weighted citation impact, top 4% of its field
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Variations in mitochondrial genome as potential prognostic markers in sickle cell disease.Haematologica · 2026Article
- Heteroplasmic variants of mitochondrial genome in tumor and normal samples from patients with hematologic malignancies.Leukemia · 2026Article
- Review
- Association of cord blood mitochondrial DNA heteroplasmy and copy number with childhood overweight or obesity.International journal of obesity (2005) · 2026Article
- Article
- Individual and joint association of maternal and cord blood mitochondrial DNA heteroplasmy and copy number with preterm birth.Pediatric research · 2026Article
- Deleterious mitochondrial heteroplasmy drives high-risk clonal hematopoiesis and hematological malignancy.medRxiv : the preprint server for health sciences · 2026Article
- Mitochondrial genetic variation across tissues of the human body.Nucleic acids research · 2026Article
- Advanced molecular techniques in distinguishing monozygotic twins for forensic applications.Genes & genomics · 2026Review
- Single-cell multi-omic analysis of mitochondrial mutational mosaicism and dynamics.Nature communications · 2026Article
- Association of mitochondrial genetic background with pS65-Ub in Lewy body disease.Acta neuropathologica · 2026Article
- Mitochondrial heteroplasmy is a risk factor for the development of chronic lymphocytic leukemia.Nature communications · 2026Article
- Associations of Blood Mitochondrial DNA Quality and Quantity with Risk of Kidney Function Decline.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Article
- Epigenome-wide association study of nuclear DNA methylation in relation to mitochondrial heteroplasmy.Nature communications · 2025Article
- Association of Epigenetic Age Acceleration and Mitochondrial DNA-Based Aging Metrics Provides Insights Into Mechanisms of Aging-Related Diseases.Aging cell · 2025Article
- Label-free robotic mitochondrial biopsy.Science advances · 2025Article
- Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations.Science (New York, N.Y.) · 2025Article
- Contributions of inherited mtDNA to longevity: evidence from extended pedigrees with 176 million kinship pairs.EBioMedicine · 2025Article
- Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).International journal of molecular medicine · 2025Review
Corrections and comments
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Authors and funding
26 authors at 13 institutions in 2 countries.
Yun Soo Hong *McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Stephanie L Battle *McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-3131-0605
Wen ShiMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-2886-2361
Daniela PuiuDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Vamsee PillalamarriMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jiaqi XieMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0001-5958-693X
Nicole J LakeDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Monkol LekDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-1227-6293
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID http://orcid.org/0000-0001-7191-1723
Stephen S RichCenter for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7986-8560
Alex P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-1427-4470
Paul L AuerDivision of Biostatistics, Institute for Health & Equity, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.ORCID http://orcid.org/0000-0003-1735-8044
Nancy Heard-CostaDepartments of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9730-0306
Chunyu LiuFramingham Heart Study, Framingham, MA, USA.
Meng LaiDepartment of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3666-838X
Joanne M MurabitoSection of General Internal Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Daniel LevyNational Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
Megan L GroveHuman Genetics Center; Department of Epidemiology, Human Genetics, and Environmental Sciences; School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID http://orcid.org/0000-0001-6764-2508
Alvaro AlonsoDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-2225-8323
Richard GibbsHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Shannon Dugan-PerezHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Lukasz P GondekDivision of Hematological Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-1551-3496
Eliseo GuallarDepartment of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Dan E ArkingMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. arking@jhmi.edu.ORCID http://orcid.org/0000-0001-8980-8695
Johns Hopkins University · USBoston University · USBaylor College of Medicine · USFred Hutch Cancer Center · USCenter for Human Genetics · USEmory University · USMedical College of Wisconsin · USNational Heart Lung and Blood Institute · USRoyal Children's Hospital · AUUCLA Medical Center · USUniversity of Minnesota · USUniversity of Virginia · USYale University · US
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MThe Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3MUCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MGenomic Architecture of Common Disease in Diverse Populations: WGS of Ongoing Hemorrhagic Stroke Study SupplementUM1HG008898 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2016 to 2020
$77.0MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MIDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MStudies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MNCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NHGRI NIH HHS U24 HG008956NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003273NHGRI NIH HHS UM1 HG008898NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201500014CNHLBI NIH HHS HHSN268201500015CNHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS K24 HL148521NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL131136NHLBI NIH HHS R01 HL144569NHLBI NIH HHS R01 HL156144NHLBI NIH HHS U01 HL120393NIA NIH HHS R01 AG059727NIDDK NIH HHS P30 DK063491
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.
Indexed as
LeukemiaMitochondriaDNA, MitochondrialHeteroplasmyHumansMutationDNA, Mitochondrial
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