Sai Zhang, Johnathan Cooper-Knock, Annika K Weimer, Minyi Shi, Lina Kozhaya, Derya Unutmaz, Calum Harvey, Thomas H Julian, Simone Furini, Elisa Frullanti, Francesca Fava, Alessandra Renieri, Peng Gao, Xiaotao Shen, Ilia Sarah Timpanaro, Kevin P Kenna, J Kenneth Baillie, Mark M Davis, Philip S Tsao, Michael P Snyder
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...
August 17, 2022: Cell Systems