CRISPRi links COVID-19 GWAS loci to LZTFL1 and RAVER1

Autor: Iris M. Fink-Baldauf, William D. Stuart, John J. Brewington, Minzhe Guo, Yutaka Maeda
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: EBioMedicine, Vol 75, Iss , Pp 103806- (2022)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2021.103806
Popis: Summary: Background: To identify host genetic variants (SNPs) associated with COVID-19 disease severity, a number of genome-wide association studies (GWAS) have been conducted. Since most of the identified variants are located at non-coding regions, such variants are presumed to affect the expression of neighbouring genes, thereby influencing COVID-19 disease severity. However, it remains largely unknown which genes are influenced by such COVID-19 GWAS loci. Methods: CRISPRi (interference)-mediated gene expression analysis was performed to identify genes functionally regulated by COVID-19 GWAS loci by targeting regions near the loci (SNPs) in lung epithelial cell lines. The expression of CRISPRi-identified genes was investigated using COVID-19-contracted human and monkey lung single-nucleus/cell (sn/sc) RNA-seq datasets. Findings: CRISPRi analysis indicated that a region near rs11385942 at chromosome 3p21.31 (locus of highest significance with COVID-19 disease severity at intron 5 of LZTFL1) significantly affected the expression of LZTFL1 (P
Databáze: Directory of Open Access Journals