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

ABSTRACT: 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 

SUBMITTER: Pillalamarri V 

PROVIDER: S-EPMC9615038 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature