PLoS ONE (Jan 2020)

Asthma and its relationship to mitochondrial copy number: Results from the Asthma Translational Genomics Collaborative (ATGC) of the Trans-Omics for Precision Medicine (TOPMed) program.

  • Maxwell P Cocco,
  • Evan White,
  • Shujie Xiao,
  • Donglei Hu,
  • Angel Mak,
  • Patrick Sleiman,
  • Mao Yang,
  • Kevin R Bobbitt,
  • Hongsheng Gui,
  • Albert M Levin,
  • Samantha Hochstadt,
  • Kyle Whitehouse,
  • Dean Rynkowski,
  • Andrea J Barczak,
  • Gonçalo Abecasis,
  • Thomas W Blackwell,
  • Hyun Min Kang,
  • Deborah A Nickerson,
  • Soren Germer,
  • Jun Ding,
  • David E Lanfear,
  • Frank Gilliland,
  • W James Gauderman,
  • Rajesh Kumar,
  • David J Erle,
  • Fernando Martinez,
  • Hakon Hakonarson,
  • Esteban G Burchard,
  • L Keoki Williams

DOI
https://doi.org/10.1371/journal.pone.0242364
Journal volume & issue
Vol. 15, no. 11
p. e0242364

Abstract

Read online

BackgroundMitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis.ObjectiveGiven the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma.MethodsWhole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing.ResultsAverage mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, PConclusionsWe observed a robust association between asthma and higher mitochondrial copy number. Asthma having an effect on mitochondria function was also supported by lower respiratory complex gene expression in this group.