Multiomic analysis reveals cell-type-specific molecular determinants of COVID-19 severity.

ABSTRACT: The determinants of severe COVID-19 in healthy adults are poorly understood, which limits the opportunity for early intervention. We present a multiomic analysis using machine learning to characterize the genomic basis of COVID-19 severity. We use single-cell multiome profiling of human lungs to link genetic signals to cell-type-specific functions. We discover >1,000 risk genes across 19 cell types, which account for 77% of the SNP-based heritability for severe disease. Genetic risk is particularly focused within natural killer (NK) cells and T cells, placing the dysfunction of these cells upstream of severe disease. Mendelian randomization and single-cell profiling of human NK cells support the role of NK cells and further localize genetic risk to CD56^bright NK cells, which are

SUBMITTER: Zhang S 

PROVIDER: S-EPMC9163145 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature