An atlas of mitochondrial DNA genotype-phenotype associations in the UK Biobank

@article{YonovaDoing2021AnAO,
  title={An atlas of mitochondrial DNA genotype-phenotype associations in the UK Biobank},
  author={Ekaterina Yonova-Doing and Claudia Calabrese and Aurora Gomez-Duran and Katherine R Schon and Wei Wei and Savita Karthikeyan and Patrick F. Chinnery and Joanna M. M. Howson},
  journal={Nature genetics},
  year={2021},
  volume={53},
  pages={982 - 993}
}
Mitochondrial genome (mtDNA) variation in common diseases has been under-explored, partly due to a lack of genotype calling and quality control procedures. Developing an at-scale workflow for mtDNA variant analyses, we show correlations between nuclear and mitochondrial genomic structures within sub-populations of Great Britain and establish a UK Biobank reference atlas of mtDNA-phenotype associations. A total of 260 mtDNA-phenotype associations were novel (P<1x10-5) including, rs2853822/m… Expand
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References

SHOWING 1-10 OF 106 REFERENCES
Investigating the relationship between mitochondrial genetic variation and cardiovascular-related traits to develop a framework for mitochondrial phenome-wide association studies
BackgroundMitochondria play a critical role in the cell and have DNA independent of the nuclear genome. There is much evidence that mitochondrial DNA (mtDNA) variation plays a role in human healthExpand
Genetic and phenotypic landscape of the mitochondrial genome in the Japanese population
TLDR
The genetic landscape of the mitochondria is described and pleiotropic mtDNA variants associated with 5 late-onset complex traits are identified and observed, including creatine kinase, in Japanese individuals from the BioBank Japan Project. Expand
Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.
TLDR
The results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease. Expand
Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases
TLDR
It is shown that mtDNA variants modifying therisk 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. Expand
Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing
TLDR
It is shown that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains. Expand
Mitochondrial DNA Backgrounds Might Modulate Diabetes Complications Rather than T2DM as a Whole
TLDR
Data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure. Expand
Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans
TLDR
Since haplogroups are defined on the basis of inherited variants, these data show that mtDNA inherited variability could play a role in successful aging and longevity. Expand
An evolutionary perspective on pathogenic mtDNA mutations: haplogroup associations of clinical disorders.
TLDR
It is suggested that, a haplogroup-group association must be detected in multiple subpopulations or in a large, carefully controlled population survey to draw broad conclusions on the basis of the available evidence. Expand
Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants
TLDR
It is shown that the respiration capacity per molecule of mtDNA in cells with the NIH3T3 or NZB mtDNA is lower than in those with the C57BL/6J, CBA/J or BALB/j mtDNA, and the genetic element underlying these differences is determined. Expand
Ancient mtDNA Genetic Variants Modulate mtDNA Transcription and Replication
TLDR
The analysis demonstrates, for the first time, the functional impact of particular mtDNA haplogroup-defining control region mutations, paving the path towards assessing the functionality of both fixed and un-fixed genetic variants in the mitochondrial genome. Expand
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