A second update on mapping the human genetic architecture of COVID-19

Canadian COVID-19 host genetics cohort replicates known severity associations

“…A power calculation (Resources) shows that in HostSeq, the power to replicate the three loci at ɑ = 0.05/3 = 0.0167 are 100%, 100% and 84.2% for chr3:45805277, chr6:41515629, and chr21:33249643, respectively. S4 Table provides a comparison between HGI7no and HostSeq for 47 of the 51 hits reported by HGI (Table 2 of [ 8 ]) that were present in HGI7no. This Table includes rs190509934 on ACE2 which is reported in HGI; this variant is not significant in HostSeq but its effect size is directionally consistent with HGI7no.…”

“… Direction and magnitude of effect size is consistent between HGI7no and HostSeq for most of the loci. Nearest-Gene and Suggested-Phenotype annotations are as provided by HGI (table S2 of HGI 2023 Nature paper) [ 8 ]. Suggested-phenotype indicates the result of HGI’s phenotypic impact assessment to determine if ‘disease severity’ or ‘infection susceptibility’ is the main impact.…”

“…While COVID-19 is caused by infection with the SARS-CoV-2 virus, work since the beginning of the pandemic has shown that human genetic variation modulates both susceptibility to infection and the severity of COVID-19. The current version of HGI, released in April 2022, found 51 loci across all phenotypic contrasts [ 8 ]. Of the 51 loci, 38 have been reported by earlier studies [ 15 – 20 ].…”

Molecular Profile of Variants Potentially Associated with Severe Forms of COVID-19 in Amazonian Indigenous Populations

“…A second new variant was also identified in IFNAR2 and the variants rs1051393, rs1131668 and rs12482556 showed high allelic frequencies in the indigenous population. Recent studies have reported the association of the IFNAR2 gene with the most severe forms of COVID-19, as well as the relationship of generic variants with more critical cases of the disease [ 26 , 27 , 28 ]. The OAS1 gene was also identified in the indigenous populations studied and five genetic variants (rs10774671, rs2660, rs7967461, rs11352835 and rs1051042) showed a high allele frequency within this population group.…”

SARS-CoV-2: An Update on the Biological Interplay with the Human Host

“…The fact that uncommon loss-of-function variants of genes involved in type I IFN immunity (especially TLR3 and TLR7) may be responsible for a more aggressive form of COVID-19 was also highlighted by Matuozzo and colleagues [79]. Overall, it can be concluded that the continuous sequencing and accurate characterization of uncommon polymorphisms would allow us to detect a number of genes that may influence both vulnerability susceptibility to SARS-CoV-2 infection as well as the severity of the resulting disease [80,81].…”