DNA methylation architecture of the ACE2 gene in nasal cells of children
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Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 enters cells via angiotensin-Converting Enzyme 2 (ACE2) receptors, highly expressed in nasal epithelium with parallel high infectivity. 1,2 The nasal epigenome is in direct contact with the environment and could explain COVID-19 disparities by reflecting social and environmental influences on ACE2 regulation. We collected nasal swabs from anterior nares of 547 children, measured DNA methylation (DNAm), and tested differences at 15 ACE2 CpGs by sex, age, race/ethnicity and epigenetic age. ACE2 CpGs were differentially methylated by sex with 12 sites having lower DNAm (mean = 12.71%) and 3 sites greater DNAm (mean = 1.45%) among females relative to males. We observed differential DNAm at 5 CpGs for Hispanic females (mean absolute difference = 3.22%) and lower DNAm at 8 CpGs for Black males (mean absolute difference = 1.33%), relative to white participants. Longer DNAm telomere length was associated with greater ACE2 DNAm at 11 and 13 CpGs among males (mean absolute difference = 7.86%) and females (mean absolute difference = 8.21%), respectively. Nasal ACE2 DNAm differences could contribute to our understanding COVID-19 severity and disparities reflecting upstream environmental and social influences. Findings need to be confirmed among adults and patients with risk factors for COVID-19 severity.
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SciScore for 10.1101/2020.08.25.20182105: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has some limitations. We do not have ACE2 expression which would inform the underlying hypothesis of epigenetic regulation. We hypothesize that the relationship between DNAm, expression and ACE2 receptors is likely …
SciScore for 10.1101/2020.08.25.20182105: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has some limitations. We do not have ACE2 expression which would inform the underlying hypothesis of epigenetic regulation. We hypothesize that the relationship between DNAm, expression and ACE2 receptors is likely complex and depends on the genomic context, cells and life-stage. The absence of age-related DNAm changes could be due to the narrow age range and young profile of our study. However, measures of epigenetic age acceleration might be more sensitive to age-related physiological changes among children as reflected in strong associations with DNAm telomere length. Although most participants in our cohort were white, the relatively large sample allowed us to test differences stratifying by sex and test differences by race/ethnicity. The epigenome is at the interface of the environment and genomic regulation. Nasal cells which are directly in contact with the environment have been shown to play a key role in SARS-CoV-2 infection. Our results demonstrate that ACE2 nasal DNAm reflects differences by sex, race/ethnicity and biological aging. The nasal epigenetic architecture of the ACE2 gene could contribute to our understanding of COVID-19 and environmental disparities. Materials and Methods:
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT02820402 Active, not recruiting Project Viva: a Longitudinal Study of Health for the Next Ge… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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