-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. -
- --The major feature of the small set of variants in this track is that they are functionally tested -to be deleterious and genetically tested to be disease-causing. Specifically, -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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