Genetic and non-genetic factors affecting the expression of COVID-19 relevant genes in the large airway epithelium
Silva Kasela; Victor E Ortega; Molly Martorella; Suresh Garudadri; Jenna Nguyen; Elizabeth Ampleford; Anu Pasanen; Srilaxmi Nerella; Kristina L Buschur; Igor Z Barjaktarevic; R Graham Barr; Eugene R Bleecker; Russell P Bowler; Alejandro P Comellas; Christopher B Cooper; David J Couper; Gerard J Criner; Jeffrey L Curtis; MeiLan K Han; Nadia N Hansel; Eric A Hoffman; Robert J Kaner; Jerry A Krishnan; Fernando J Martinez; Merry-Lynn N McDonald; Deborah A Meyers; Robert Paine III; Stephen P Peters; Mario Castro; Loren C Denlinger; Serpil C Erzurum; John V Fahy; Elliot Israel; Nizar N Jarjour; Bruce D Levy; Xingnan Li; Wendy C Moore; Sally E Wenzel; Joe Zein; - NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS); - NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Charles Langelier; Prescott G Woodruff; Tuuli Lappalainen; Stephanie A Christenson.
Preprint
en Inglés
| PREPRINT-MEDRXIV | ID: ppmedrxiv-20202820
Introductory paragraphParticular host and environmental factors influence susceptibility to severe COVID-19. We analyzed RNA-sequencing data from bronchial epithelial brushings - a relevant tissue for SARS-CoV-2 infection - obtained from three cohorts of uninfected individuals, and investigated how non-genetic and genetic factors affect the regulation of host genes implicated in COVID-19. 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.
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