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Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number by Vamsee Pillalamarri; Wen Shi; Conrad Say; Stephanie Yang; John Lane; Eliseo Guallar; Nathan Pankratz; Dan E. Arking is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number about?

## Summary Inter-individual variation in the number of copies of the mitochondrial genome, called mitochondrial DNA copy number (mtDNA-CN), reflects mitochondrial function and has been associated with various aging-related diseases. We examined 415,422 exomes of self-reported White ancestry individuals from the UK Biobank and tested the impact of rare variants, at the level of single variants and through aggregate variant-set tests, on mtDNA-CN. A survey across nine variant sets tested enrichment of putatively causal variants and identified 14 genes at experiment-wide significance and three genes at marginal significance. These included associations at known mtDNA depletion syndrome genes (mtDNA helicase __TWNK__, p = 1.1 × 10^−30^; mitochondrial transcription factor __TFAM__, p = 4.3 × 10^−15^; mtDNA maintenance exonuclease __MGME1__, p = 2.0 × 10^−6^) and the V617F dominant gain-of-function mutation in the tyrosine kinase __JAK2__ (p = 2.7 × 10^−17^), associated with myeloproliferative disease. Novel genes included the ATP-dependent protease __CLPX__ (p = 8.4 × 10^−9^), involved in mitochondrial proteome quality, and the mitochondrial adenylate kinase __AK2__ (p = 4.7 × 10^−8^),

Who reads Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number?

Author

Vamsee Pillalamarri; Wen Shi; Conrad Say; Stephanie Yang; John Lane; Eliseo Guallar; Nathan Pankratz; Dan E. Arking

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)