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 DingDav E. Lanfear, Frank Gilliland, W. James Gauderman, Rajesh Kumar, Dav J. Erle, Fernando Martinez, Hakon Hakonarson, Esteban G. Burchard, L. Keoki Williams

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis. Objective Given 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. Methods Whole 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. Results Average mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P<0.001; SAGE II: 235.99 vs. 223.07, P<0.001). Asthma status was significantly associated with mitochondrial copy number after accounting for potential explanatory variables, such as participant age, sex, leukocyte counts, and mitochondrial haplogroup. Despite the consistent relationship between asthma status and mitochondrial copy number, the latter was not associated with time-to-exacerbation or patient-reported asthma control. Mitochondrial respiratory complex gene expression was disproportionately lower in individuals with asthma when compared with individuals without asthma and other protein-encoding genes. Conclusions We 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.

Original languageEnglish (US)
Article numbere0242364
JournalPloS one
Issue number11 November
StatePublished - Nov 2020

ASJC Scopus subject areas

  • General


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