ArticleInternational journal of molecular sciences2026
Disentangling Shared and Differential Genetic Architectures Between COVID-19 and Other Respiratory Disorders-A Genome-Wide Multi-Omics Framework.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
A bidirectional relationship has been observed between COVID-19 and respiratory disorders, where respiratory comorbidities increase severity, and COVID-19 induces respiratory sequelae. The underlying biological and genetic mechanisms remain unclear. While previous studies have identified overlapping genetic loci, few have systematically disentangled the genetic factors shared between these conditions versus those specific to COVID-19, particularly at a multi-omics level. We developed and applied a unified analytical framework to compare three COVID-19 phenotypes with eight respiratory disorders (including asthma, COPD, IPF, and pneumonia). Utilizing the cofdr method for shared genetic signal analysis and DDx/mtCOJO for differentiation, we integrated genome-wide association statistics with multi-omics data (transcriptome, splicing, and proteome). This approach allowed for the simultaneous identification of shared genetic signals (concordant or discordant) and disease-specific variants across expression (TWAS), alternative splicing (spTWAS), and protein abundance (PWAS). We delineated a comprehensive atlas of 214 differential and numerous shared loci across 24 pairwise comparisons. The shared genetic architecture was characterized by pleiotropic effects in genes such as
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