Evaluation of mitochondrial DNA copy number estimation techniques.

TitleEvaluation of mitochondrial DNA copy number estimation techniques.
Publication TypeJournal Article
Year of Publication2020
AuthorsLongchamps, RJ, Castellani, CA, Yang, SY, Newcomb, CE, Sumpter, JA, Lane, J, Grove, ML, Guallar, E, Pankratz, N, Taylor, KD, Rotter, JI, Boerwinkle, E, Arking, DE
JournalPLoS One
Volume15
Issue1
Paginatione0228166
Date Published2020
ISSN1932-6203
KeywordsAged, DNA, Mitochondrial, Female, Gene Dosage, Genomics, Humans, Male, Middle Aged
Abstract

Mitochondrial DNA copy number (mtDNA-CN), a measure of the number of mitochondrial genomes per cell, is a minimally invasive proxy measure for mitochondrial function and has been associated with several aging-related diseases. Although quantitative real-time PCR (qPCR) is the current gold standard method for measuring mtDNA-CN, mtDNA-CN can also be measured from genotyping microarray probe intensities and DNA sequencing read counts. To conduct a comprehensive examination on the performance of these methods, we use known mtDNA-CN correlates (age, sex, white blood cell count, Duffy locus genotype, incident cardiovascular disease) to evaluate mtDNA-CN calculated from qPCR, two microarray platforms, as well as whole genome (WGS) and whole exome sequence (WES) data across 1,085 participants from the Atherosclerosis Risk in Communities (ARIC) study and 3,489 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). We observe mtDNA-CN derived from WGS data is significantly more associated with known correlates compared to all other methods (p

DOI10.1371/journal.pone.0228166
Alternate JournalPLoS One
PubMed ID32004343
PubMed Central IDPMC6994099
Grant ListN01 HC095163 / HC / NHLBI NIH HHS / United States
N01 HC095168 / HC / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
N01 HC095165 / HC / NHLBI NIH HHS / United States
N01 HC095169 / HC / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
N01 HC095166 / HC / NHLBI NIH HHS / United States
N02HL64278 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
N01 HC095167 / HC / NHLBI NIH HHS / United States
N01 HC095164 / HC / NHLBI NIH HHS / United States
N01 HC095160 / HC / NHLBI NIH HHS / United States
T32 GM007814 / GM / NIGMS NIH HHS / United States
HHSN263201500003I / NH / NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
N01 HC095162 / HC / NHLBI NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States
P30 AG021334 / AG / NIA NIH HHS / United States
N01 HC095161 / HC / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
R01 HL131573 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States