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Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases

Lookup NU author(s): Professor Gavin Hudson, Dr Aurora Gomez Duran, Dr Ian Wilson, Professor Patrick Chinnery



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Hudson G, Gomez-Duran A, Wilson IJ, Chinnery PF

Publication type: Article

Publication status: Published

Journal: PLoS Genetics

Year: 2014

Volume: 10

Issue: 5

Print publication date: 22/05/2014

Online publication date: 22/05/2014

Acceptance date: 24/03/2014

Date deposited: 27/08/2014

ISSN (print): 1553-7390

ISSN (electronic): 1553-7404

Publisher: Public Library of Science


DOI: 10.1371/journal.pgen.1004369


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Funder referenceFunder name
Henry Smith Charity
National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University
UK Blood Services Collection of Common Controls - Wellcome Trust
068545Wellcome Trust
096919Z/11/ZWellcome Trust Centre for Mitochondrial Research
G0000934Medical Research Council
G0601943Medical Research Council (UK) Centre for Translational Muscle Disease research
101876/Z/13/ZWellcome Trust