Genetic mechanisms of critical illness in Covid-19

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC （Genetics Of Mortality In Critical Care） genome-wide association study（GWAS） in 2244 critically ill Covid-19 patients from 208 UK intensive care units （ICUs）. We identify and replicate novel genome-wide significant associations, on chr12q24.13 （rs10735079, p=1.65 [Formula:see text] 10-8） in a gene cluster encoding antiviral restriction enzyme activators （OAS1, OAS2, OAS3）, on chr19p13.2 （rs2109069, p=2.3 [Formula:see text] 10-12） near the gene encoding tyrosine kinase 2 （TYK2）, on chr19p13.3 （rs2109069, p=3.98 [Formula:see text] 10-12） within the gene encoding dipeptidyl peptidase 9 （DPP9）, and on chr21q22.1 （rs2236757, p=4.99 [Formula:see text] 10-8） in the interferon receptor gene IFNAR2.