Description
Vamsee Pillalamarri will discuss the impact of rare nuclear genetic variation on the number of copies of the mitochondrial genome, called mitochondrial DNA copy number (mtDNA-CN), an important biomarker for aging. Results from the study implicate an ancestral haplotype associated with increased mtDNA-CN, as well as highlight core processes involved with mtDNA replication and maintenance and enrichment of rare variant associations in Mendelian mtDNA depletion syndromes loci.
Learning Objectives
- Highlight the association of mitochondrial DNA copy number with aging related traits and disease
- Describe the use of whole-exome sequencing and genotyping data to estimate the number of copies of the mitochondrial genome in the UK Biobank
- Perform an exome-wide association study of single-variant and gene-based groups of rare variants with mtDNA-CN
- Identify 24 independent signals from 17 loci
- Rare variants delineate a 1.2 Mb ancestral haplotype associated with increased mtDNA-CN, contrary to expectation that physically distant rare variants are in linkage equilibrium
- mtDNA-CN associated rare variants are enriched in loci implicated in Mendelian mtDNA depletion syndromes
