ArticleGenome research2021
Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease.
Article in Genome research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 5 of them syntheses that pooled it.
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Who cites it
67 citing papers in PubMed, 5 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.European journal of neurology · 2025Pooled it
- Whole blood mitochondrial copy number in clinical populations with mood disorders: A meta-analysis: Blood mitochondrial copy number and mood disorders.Psychiatry research · 2024Pooled it
- Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function: A Meta-analysis of Community-Based Cohorts.Neurology · 2023Pooled it
- Comprehensive summary of mitochondrial DNA alterations in the postmortem human brain: A systematic review.EBioMedicine · 2022Pooled it
- Epigenome-wide association study of mitochondrial genome copy number.Human molecular genetics · 2021Pooled it
- Lower mitochondrial DNA copy number in ATTRV50M Swedish carriers.Orphanet journal of rare diseases · 2026Article
- Reduced Mitochondrial DNA Copy Number and Telomere Length in Essential Tremor Patients: Evidence from an Age- and Sex-Adjusted Cross-Sectional Case-Control Study.International journal of molecular sciences · 2026Article
- Transcriptomic analysis of cells following decreased mitochondrial DNA-copy number reveals compensatory mechanisms in mitochondrial DNA replication and cellular energetics.Experimental cell research · 2026Article
- Association between blood mitochondrial DNA copy number and cognitive function: A cross-sectional study based on the Yakumo Study.Fujita medical journal · 2026Article
- Association of leukocyte mitochondrial DNA copy number and inflammation with mortality among older adults.Communications medicine · 2026Article
- Intergenerational and organ-specific alterations in mitochondrial DNA copy number following preconception irradiation.Redox biology · 2026Article
- Mitochondrial DNA copy number reduction viaEpigenomics · 2026Article
- Gestational phthalate levels and biomarkers of aging in infants and children from New York City.Environmental research · 2025Article
- Transcriptomic analysis of cells following decreased mitochondrial DNA-copy number reveals compensatory mechanisms in mitochondrial DNA replication and cellular energetics.bioRxiv : the preprint server for biology · 2025Article
- Insights into the Biomarker Potential of Humanin and Mots-c Expression and Telomere Length in Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Cord Blood Mitochondrial DNA Copy Number and Physical Growth in Infancy and Toddlerhood: A Birth Cohort Analysis.Children (Basel, Switzerland) · 2025Article
- Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.World journal of methodology · 2025Review
- Associations of maternal neighborhood and trauma-related stressors with mitochondrial DNA copy number and telomere length in maternal and cord blood.Scientific reports · 2025Article
- Cell cycle- and dose-dependent effects on mitochondrial DNA copy number variation following irradiation.Journal of cell science · 2025Article
- Dynamics of mitochondrial DNA copy number regulation in relation to gastric cancer survival.Discover oncology · 2025Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial DNA copy number (mtDNA-CN) is a proxy for mitochondrial function and is associated with aging-related diseases. However, it is unclear how mtDNA-CN measured in blood can reflect diseases that primarily manifest in other tissues. Using the Genotype-Tissue Expression Project, we interrogated relationships between mtDNA-CN measured in whole blood and gene expression from whole blood and 47 additional tissues in 419 individuals. mtDNA-CN was significantly associated with expression of 700 genes in whole blood, including nuclear genes required for mtDNA replication. Significant enrichment was observed for splicing and ubiquitin-mediated proteolysis pathways, as well as target genes for the mitochondrial transcription factor NRF1. In nonblood tissues, there were more significantly associated genes than expected in 30 tissues, suggesting that global gene expression in those tissues is correlated with blood-derived mtDNA-CN. Neurodegenerative disease pathways were significantly associated in multiple tissues, and in an independent data set, the UK Biobank, we observed that higher mtDNA-CN was significantly associated with lower rates of both prevalent (OR = 0.89, CI = 0.83; 0.96) and incident neurodegenerative disease (HR = 0.95, 95% CI = 0.91;0.98). The observation that mtDNA-CN measured in blood is associated with gene expression in other tissues suggests that blood-derived mtDNA-CN can reflect metabolic health across multiple tissues. Identification of key pathways including splicing, RNA binding, and catalysis reinforces the importance of mitochondria in maintaining cellular homeostasis. Finally, validation of the role of mtDNA CN in neurodegenerative disease in a large independent cohort study solidifies the link between blood-derived mtDNA-CN, altered gene expression in multiple tissues, and aging-related disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.