Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases
Year: 2014
Type: article
Study design: Observational Study
Abstract: Mitochondrial DNA (mtDNA) is highly polymorphic at the population level, and specific mtDNA variants affect mitochondrial function. With emerging evidence that mitochondrial mechanisms are central to common human diseases, it is plausible that mtDNA variants contribute to the "missing heritability" of several complex traits. Given the central role of mtDNA genes in oxidative phosphorylation, the same genetic variants would be expected to alter the risk of developing several different disorders, but this has not been shown to date. Here we studied 38,638 individuals with 11 major diseases, and 17,483 healthy controls. Imputing missing variants from 7,729 complete mitochondrial genomes, we captured 40.41% of European mtDNA variation. We show that mtDNA variants modifying the risk of developing one disease also modify the risk of developing other diseases, thus providing independent replication of a disease association in different case and control cohorts. High-risk alleles were more common than protective alleles, indicating that mtDNA is not at equilibrium in the human population, and that recent mutations interact with nuclear loci to modify the risk of developing multiple common diseases.
Source: PLoS Genetics
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,110
Funders: Wellcome Trust, National Institute for Health and Care Research, Parkinson's UK, Newcastle University, Henry Smith Charity, Newcastle upon Tyne Hospitals NHS Foundation Trust, Medical Research Council, NIHR Newcastle Biomedical Research Centre, Wellcome Trust Centre for Mitochondrial Research
Awards: G105456294, G1332667197, MICA: MRC Centre for Neuromuscular Diseases, Mitochondrial DNA - expression, disease and treatment., Mitochondrial DNA - expression, disease and treatment., Genetic factors modulating the expression of mitochondrial disease., G2953502109, G3349769430, G4335143496, G4702529995, Genetic factors modulating the expression of mitochondrial disease., G5568298347, A national DNA control series for genetic case-control studies based on the British 1958 birth cohort, G7551989283, G7556113848, G7691820597, G8538723892, G8653647586
OpenAlex ID: W1987954830