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WSB1 (HGNC:19221) has been implicated as one of several susceptibility loci contributing to the risk of COVID‑19 related mortality (MONDO:0100096). Two independent studies performed a genome‑wide association study (GWAS) in a UK Biobank cohort of infected cases and identified super variants that include WSB1 as a risk factor for death. In the discovery phase involving 1,778 cases with 445 deaths (PMID:33200144), the analysis suggested that genetic variation at this locus may contribute to heterogeneous outcomes among patients. The subsequent validation study (PMID:33536081) confirmed the association in a comparable cohort, underscoring the potential clinical relevance of this finding.
The genetic evidence supporting the association relies on aggregate groups of variants—termed super variants—that collectively harbor risk signals. Although the studies do not report a single, definitive coding change in WSB1, the robust replication across independent cohorts adds weight to the association. No explicit family segregation or classical Mendelian inheritance was reported, which is expected given the complex, multifactorial nature of COVID‑19 susceptibility.
Due to the multifactorial basis of COVID‑19 risk, the mode of inheritance for this association is best described as complex. While the GWAS approach captures the cumulative effects of multiple variants, traditional segregation analysis is not applicable. Consequently, the evidence is derived from population‐based associations rather than familial studies.
A review of the variant-level data revealed no specific HGVS‑formatted coding variants for WSB1 in the context of COVID‑19. Therefore, no individual variant meeting the criteria (e.g., a complete coding change with both “c.” and “(p…)” components) is available from the provided evidence. The reported genetic signal is attributable to the aggregated effect of multiple loci within the super variant framework.
There is limited direct experimental evidence linking WSB1 functionally to COVID‑19 pathophysiology. Although related functional studies have been performed in other disease contexts (such as neuroblastoma, Parkinson disease, and cancer), these do not provide direct mechanistic insight into how WSB1 variation modulates COVID‑19 outcomes. Consequently, while the genetic data indicate an association, further functional studies are needed to elucidate the biological mechanism underlying this risk.
In conclusion, the integrated data from two independent GWAS support a moderate association between WSB1 and increased risk of COVID‑19 mortality. This association, despite the absence of a single clearly pathogenic variant and direct functional evidence, represents a promising avenue for further research and holds potential clinical utility for risk stratification in COVID‑19 management.
Gene–Disease AssociationModerateTwo independent GWAS studies of 1,778 cases (445 deaths) (PMID:33200144, PMID:33536081) consistently identified super variants including WSB1, supporting a modest association with COVID‑19 mortality. Genetic EvidenceModerateThe aggregate super variant analysis implicates WSB1 in COVID‑19 mortality risk despite the absence of a single definitive coding variant, meeting criteria for moderate genetic support. Functional EvidenceLimitedNo direct functional assays or mechanistic studies linking WSB1 to COVID‑19 pathogenesis were provided, although functional studies in other diseases suggest biological relevance. |