ArticleProceedings of the National Academy of Sciences of the United States of America2014
Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
155 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Systematic review of Leber's hereditary optic neuropathy - Clinical diagnosis, genetics overview and current concepts of treatment.Indian journal of ophthalmology · 2026Pooled it
- Human studies of mitochondrial biology demonstrate an overall lack of binary sex differences: A multivariate meta-analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Pooled it
- Shifting the Balance: Mitochondrial Heteroplasmy as a Driver of Cardiac Disease.Circulation research · 2026Review
- Mitochondrial Dysfunction in Autism and Attention-Deficit/Hyperactivity Disorder: Evidence from Genetic, Biochemical, and Neuroimaging Approaches.Antioxidants (Basel, Switzerland) · 2026Review
- Mito_Plot: open-source pipeline for quantification and visualization of mitochondrial DNA heteroplasmy.BMC bioinformatics · 2026Article
- ASSOCIATION ANALYSIS OF MITOCHONDRIAL HETEROPLASMIC VARIANTS AND CARDIOMETABOLIC TRAITS.medRxiv : the preprint server for health sciences · 2026Article
- Rethinking medical education through systems biology to address complexity.NPJ systems biology and applications · 2026Review
- Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- The nuclear and mitochondrial genomes need to tango. How is their dance synchronized during development?NAR molecular medicine · 2026Article
- Clinical Validation of Digital PCR for Precise m.3243A>G Heteroplasmy Quantification in Early-Onset Diabetes.Journal of diabetes research · 2026Article
- Mitochondrial haplogroups, but not heteroplasmy, are associated with midlife cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Pervasive non-random mitochondrial DNA heteroplasmy in the hybrid water frog Pelophylax esculentus.BMC ecology and evolution · 2025Article
- Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).International journal of molecular medicine · 2025Review
- The interplay between mitochondrial DNA genotypes, female infertility, ovarian response, and mutagenesis in oocytes.Human reproduction open · 2025Article
- Exploring the oncogenic impact of heteroplasmicMitochondrial communications · 2025Article
- Mitochondrial Transplantation: A Paradigm Shift in Osteoporosis Therapy.International journal of nanomedicine · 2025Review
- Mitochondrial DNA Damage and Its Repair Mechanisms in Aging Oocytes.International journal of molecular sciences · 2024Review
- The quality and detection limits of mitochondrial heteroplasmy by long read nanopore sequencing.Scientific reports · 2024Article
- Association analysis of mitochondrial DNA heteroplasmic variants: Methods and application.Mitochondrion · 2024Article
- Massively parallel sequencing of mitochondrial genome in primary open angle glaucoma identifies somatically acquired mitochondrial mutations in ocular tissue.Scientific reports · 2024Article
95 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
5 authors.
Funding
Abstract
A majority of mitochondrial DNA (mtDNA) mutations reported to be implicated in diseases are heteroplasmic, a status with coexisting mtDNA variants in a single cell. Quantifying the prevalence of mitochondrial heteroplasmy and its pathogenic effect in healthy individuals could further our understanding of its possible roles in various diseases. A total of 1,085 human individuals from 14 global populations have been sequenced by the 1000 Genomes Project to a mean coverage of ∼2,000× on mtDNA. Using a combination of stringent thresholds and a maximum-likelihood method to define heteroplasmy, we demonstrated that ∼90% of the individuals carry at least one heteroplasmy. At least 20% of individuals harbor heteroplasmies reported to be implicated in disease. Mitochondrial heteroplasmy tend to show high pathogenicity, and is significantly overrepresented in disease-associated loci. Consistent with their deleterious effect, heteroplasmies with derived allele frequency larger than 60% within an individual show a significant reduction in pathogenicity, indicating the action of purifying selection. Purifying selection on heteroplasmies can also be inferred from nonsynonymous and synonymous heteroplasmy comparison and the unfolded site frequency spectra for different functional sites in mtDNA. Nevertheless, in comparison with population polymorphic mtDNA mutations, the purifying selection is much less efficient in removing heteroplasmic mutations. The prevalence of mitochondrial heteroplasmy with high pathogenic potential in healthy individuals, along with the possibility of these mutations drifting to high frequency inside a subpopulation of cells across lifespan, emphasizes the importance of managing mitochondrial heteroplasmy to prevent disease progression.
Indexed as
Identifiers
What OpenQuestion holds
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.