Journal article
Genetic and non-genetic factors affecting the expression of COVID-19-relevant genes in the large airway epithelium
Genome medicine, Vol.13(1), pp.66-66
04/21/2021
DOI: 10.1186/s13073-021-00866-2
PMCID: PMC8059115
PMID: 33883027
Abstract
The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression.
We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with and without chronic obstructive pulmonary disease (COPD) and replicated these associations in two asthma cohorts, SARP and MAST. To identify airway biology beyond ACE2 binding that may contribute to increased susceptibility, we used gene set enrichment analyses to determine if gene expression changes indicative of a suppressed airway immune response observed early in SARS-CoV-2 infection are also observed in association with host factors. To identify host genetic variants affecting COVID-19 susceptibility in SPIROMICS, we performed expression quantitative trait (eQTL) mapping and investigated the phenotypic associations of the eQTL variants.
We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections.
These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.
Details
- Title: Subtitle
- Genetic and non-genetic factors affecting the expression of COVID-19-relevant genes in the large airway epithelium
- Creators
- Silva Kasela - Columbia UniversityVictor E Ortega - Wake Forest UniversityMolly Martorella - Columbia UniversitySuresh Garudadri - Stanford UniversityJenna Nguyen - University of California, San FranciscoElizabeth Ampleford - Wake Forest UniversityAnu Pasanen - Columbia UniversitySrilaxmi Nerella - University of California, San FranciscoKristina L Buschur - Columbia University Irving Medical CenterIgor Z Barjaktarevic - University of California, Los AngelesR Graham Barr - Columbia University Irving Medical CenterEugene R Bleecker - University of ArizonaRussell P Bowler - National Jewish HealthAlejandro P Comellas - University of IowaChristopher B Cooper - University of California, Los AngelesDavid J Couper - University of North Carolina at Chapel HillGerard J Criner - Temple UniversityJeffrey L Curtis - University of MichiganMeiLan K Han - University of MichiganNadia N Hansel - Johns Hopkins UniversityEric A Hoffman - University of IowaRobert J Kaner - Weill Cornell MedicineJerry A Krishnan - University of Illinois ChicagoFernando J Martinez - Weill Cornell MedicineMerry-Lynn N McDonald - University of Alabama at BirminghamDeborah A Meyers - University of ArizonaRobert Paine III - University of UtahStephen P Peters - Wake Forest UniversityMario Castro - University of KansasLoren C Denlinger - University of Wisconsin–MadisonSerpil C Erzurum - Cleveland ClinicJohn V Fahy - University of California, San FranciscoElliot Israel - Brigham and Women's HospitalNizar N Jarjour - University of Wisconsin–MadisonBruce D Levy - Brigham and Women's HospitalXingnan Li - University of ArizonaWendy C Moore - Wake Forest UniversitySally E Wenzel - University of PittsburghJoe Zein - Cleveland ClinicCharles Langelier - University of California, San FranciscoPrescott G Woodruff - University of California, San FranciscoTuuli Lappalainen - Columbia UniversityStephanie A Christenson - University of California, San FranciscoNHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS)
- Contributors
- Karin F Hoth (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- Genome medicine, Vol.13(1), pp.66-66
- DOI
- 10.1186/s13073-021-00866-2
- PMID
- 33883027
- PMCID
- PMC8059115
- NLM abbreviation
- Genome Med
- ISSN
- 1756-994X
- eISSN
- 1756-994X
- Grant note
- R01 HL142028 / NHLBI NIH HHS R01HL142992 / NHLBI NIH HHS R01MH106842 / NIMH NIH HHS U19 AI077439 / NIAID NIH HHS U01 HL137880 / NHLBI NIH HHS K01 AG059898 / NIA NIH HHS K08 HL141601 / NHLBI NIH HHS R01HL137880 / NHLBI NIH HHS K23 HL138461 / NHLBI NIH HHS K24 HL137013 / NHLBI NIH HHS U01HL137880 / NHLBI NIH HHS R01GM124486 / NIGMS NIH HHS P30 ES010126 / NIEHS NIH HHS R01GM122924 / NIGMS NIH HHS K23HL123778 / NHLBI NIH HHS K23 HL123778 / NHLBI NIH HHS P01 HL107202 / NHLBI NIH HHS T32 HL144442 / NHLBI NIH HHS R01HL142028 / NHLBI NIH HHS F30HG011194 / NHGRI NIH HHS UM1HG008901 / NHGRI NIH HHS R01HL121774 / NHLBI NIH HHS T32HL144442 / NHLBI NIH HHS
- Language
- English
- Date published
- 04/21/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Pulmonary, Critical Care, and Occupational Medicine; Psychiatry; ICTS; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984293752702771
Metrics
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