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Genet."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>COVID-19 severity has been linked to immune factors, with excessive immune responses like cytokine storms contributing to mortality. However, the genetic basis of these immune responses is not well understood. This study aimed to explore the genetic connection between COVID-19 severity and blood cell traits, given their close relationship with immunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>GWAS summary statistics for COVID-19 and blood cell counts were analyzed using Linkage Disequilibrium Score Regression (LDSC) to estimate genetic correlations and heritabilities. For traits with significant correlations, a Multi-Trait GWAS Analysis (MTAG) was performed to identify pleiotropic loci shared between COVID-19 and blood cell counts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our MTAG analysis identified four pleiotropic loci associated with COVID-19 severity, five loci linked to hospitalized cases, and one locus related to general patients. Among these, two novel loci were identified in the high-risk population, with rs55779981 located near <jats:italic>RAVER1<\/jats:italic> and rs73009538 near <jats:italic>CARM1<\/jats:italic>. In hospitalized patients, two previously unrecognized loci were detected, namely, rs115545251 near <jats:italic>GFI1<\/jats:italic> and rs3181049 near <jats:italic>RAVER1<\/jats:italic>, while in general patients, rs11065822 near <jats:italic>CUX2<\/jats:italic> emerged as a newly identified locus. We also identified potential target genes, including those involved in inflammation signaling (<jats:italic>CARM1<\/jats:italic>), endothelial dysfunction (<jats:italic>INTS12<\/jats:italic>), and antiviral immune response (<jats:italic>RAVER1<\/jats:italic>), which may require further investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study offers insights into the genetic overlap between COVID-19 and immune factors, suggesting potential directions for future research and clinical exploration.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1502839","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T06:49:38Z","timestamp":1739774978000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring genetic loci linked to COVID-19 severity and immune response through multi-trait GWAS analyses"],"prefix":"10.3389","volume":"16","author":[{"given":"Ziang","family":"Meng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chumeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bichen","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1001\/jama.2021.7212","article-title":"Researchers tie severe immunosuppression to chronic COVID-19 and virus variants","volume":"325","author":"Abbasi","year":"2021","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1146\/annurev-immunol-041015-055459","article-title":"Immunobiology of long noncoding RNAs","volume":"35","author":"Atianand","year":"2017","journal-title":"Annu. 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