Author: Satria P. Sajuthi; Peter DeFord; Nathan D. Jackson; Michael T. Montgomery; Jamie L. Everman; Cydney L. Rios; Elmar Pruesse; James D. Nolin; Elizabeth G. Plender; Michael E. Wechsler; Angel CY Mak; Celeste Eng; Sandra Salazar; Vivian Medina; Eric M. Wohlford; Scott Huntsman; Deborah A. Nickerson; Soren Germer; Michael C. Zody; Gonçalo Abecasis; Hyun Min Kang; Kenneth M. Rice; Rajesh Kumar; Sam Oh; Jose Rodriguez-Santana; Esteban G. Burchard; Max A. Seibold
Title: Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium Document date: 2020_4_10
ID: mj8ebo7i_5
Snippet: Namely, the allele frequency of rs74659079 is above 1% only among people of African 292 descent (AF=11%) and 4% in the participating Puerto Rican population. Likewise, the 293 rs2838057 eQTL variant, which was associated with increased TMPRSS2 expression 294 was present at a frequency of 32% in East Asians, 20% in Latinos, and <10% in all 295 other world populations. Together, these results suggest that if TMPRSS2 levels 296 influence susceptibil.....
Document: Namely, the allele frequency of rs74659079 is above 1% only among people of African 292 descent (AF=11%) and 4% in the participating Puerto Rican population. Likewise, the 293 rs2838057 eQTL variant, which was associated with increased TMPRSS2 expression 294 was present at a frequency of 32% in East Asians, 20% in Latinos, and <10% in all 295 other world populations. Together, these results suggest that if TMPRSS2 levels 296 influence susceptibility to SARS-CoV-2, then genetics may play a significant role in 297 infection risk and that this risk will vary significantly across world populations. Our analyses indicate that T2 inflammation, interferon/viral response signaling, and 303 genetics are all determinants of ACE2 and TMPRSS2 gene expression in the airway 304 epithelium of children. Therefore, we next sought to determine the relative importance of 305 these factors in determining levels of these genes using multi-variable regression 306 analysis. We included asthma status, age, and sex as model covariates since chronic 307 . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.09.034454 doi: bioRxiv preprint lung disease, increasing age, and male sex have all been associated with increased risk 308 of poor COVID-19 illness outcomes. Modeling ACE2 expression among GALA II 309 children, we found that T2 and interferon statuses had the strongest effects on ACE2 310 expression (p=1.6e-57, p=6.5e-43, respectively), with T2-low and interferon-high 311 individuals exhibiting the highest levels of expression. These two variables 312 independently explained 24% and 17% of the variance in ACE2 expression (Table 1) . 313
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