+This track shows variants associated with monogenic congenital defects of immunity to SARS-CoV-2, +with incomplete or complete penetrance from the COVID Human Genetic Effort. This international consortium aims +to detect rare or common monogenic inborn immunity errors (IEI) underlying severe forms of COVID-19 +in previously healthy individuals, as well as rare or common monogenic variations that make certain +individuals resistant to the infection by SARS-CoV2 itself despite repeated exposure. +
+ ++Rare variants were predicted to be loss-of-function (LOF) at 13 human loci known to govern +TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus in patients with +life-threatening COVID-19 pneumonia, relative to subjects with asymptomatic or benign infection. +These genetic defects display incomplete penetrance for influenza respiratory distress and only +manifested clinically upon infection with the more virulent SARS-CoV-2. +
+ ++Variant calls in 12 autosomal IFN-related genes from whole exome or genome data with a MAF lower +than 0.001 (gnomAD v2.1.1) and experimental demonstration of loss-of-function (LOF) were considered +for statistical analysis. Proportion of individuals carrying at least one pLOF variant was compared +between cases and controls by means of logistic regression with the likelihood ratio test. The first +three principal components of the PCA were included in the logistic regression model to account for +ethnic heterogeneity of the cohorts. Analysis of enrichment in rare (MAF < 0.001) synonymous +variants of the 12 genes was performed to check the calibration of the burden test. PCA war +conducted with Plink v1.9 software on whole exome and genome sequencing data and 1000 Genomes (1kG) +Project phase 3 public database as reference, using 27,480 exonic variants with a minor allele +frequency >0.01 and a call rate >0.99. The odds ratio was also estimated by logistic regression +and adjusted for ethnic heterogeneity. +
+ ++The raw data can be explored interactively with the +Table Browser, or the Data Integrator. +Please refer to +our mailing list archives for questions, or our Data Access FAQ for more information. +
+ ++Thanks to the COVID Human Genetic Effort contributors for making these data available, and in +particular to Qian Zhang at the Rockefeller University for review and input during browser track +development. +
+ + ++Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C +et al. + +Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. +Science. 2020 Sep 24;. +PMID: 32972995 +
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