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.
Author
Cocco, Maxwell PWhite, Evan
Xiao, Shujie
Hu, Donglei
Mak, Angel
Sleiman, Patrick
Yang, Mao
Bobbitt, Kevin R
Gui, Hongsheng
Levin, Albert M
Hochstadt, Samantha
Whitehouse, Kyle
Rynkowski, Dean
Barczak, Andrea J
Abecasis, Gonçalo
Blackwell, Thomas W
Kang, Hyun Min
Nickerson, Deborah A
Germer, Soren
Ding, Jun
Lanfear, David E
Gilliland, Frank
Gauderman, W James
Kumar, Rajesh
Erle, David J
Martinez, Fernando
Hakonarson, Hakon
Burchard, Esteban G
Williams, L Keoki
Affiliation
Univ Arizona, Arizona Resp CtrUniv Arizona, Dept Pediat
Issue Date
2020-11-25
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PUBLIC LIBRARY SCIENCECitation
Cocco, M. P., White, E., Xiao, S., Hu, D., Mak, A., Sleiman, P., ... & Williams, L. K. (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. PloS one, 15(11), e0242364.Journal
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© 2020 Cocco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
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.Note
Open access journalISSN
1932-6203EISSN
1932-6203PubMed ID
33237978Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0242364
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Except where otherwise noted, this item's license is described as © 2020 Cocco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.