Academic Journal
Stratified analyses refine association between TLR7 rare variants and severe COVID-19
| العنوان: | Stratified analyses refine association between TLR7 rare variants and severe COVID-19 |
|---|---|
| المؤلفون: | Boos, Jannik, van der Made, Caspar I, Ramakrishnan, Gayatri, Coughlan, Eamon, Asselta, Rosanna, Löscher, Britt-Sabina, Valenti, Luca V C, de Cid, Rafael, Bujanda, Luis, Julià, Antonio, Pairo-Castineira, Erola, Baillie, J Kenneth, May, Sandra, Zametica, Berina, Heggemann, Julia, Albillos, Agustín, Banales, Jesus M, Barretina, Jordi, Blay, Natalia, Bonfanti, Paolo, Buti, Maria, Fernandez, Javier, Marsal, Sara, Prati, Daniele, Ronzoni, Luisa, Sacchi, Nicoletta, Schultze, Joachim L, Riess, Olaf, Franke, Andre, Rawlik, Konrad, Ellinghaus, David, Hoischen, Alexander, Schmidt, Axel, Ludwig, Kerstin U |
| المساهمون: | Boos, J, van der Made, C, Ramakrishnan, G, Coughlan, E, Asselta, R, Löscher, B, Valenti, L, de Cid, R, Bujanda, L, Julià, A, Pairo-Castineira, E, Baillie, J, May, S, Zametica, B, Heggemann, J, Albillos, A, Banales, J, Barretina, J, Blay, N, Bonfanti, P, Buti, M, Fernandez, J, Marsal, S, Prati, D, Ronzoni, L, Sacchi, N, Schultze, J, Riess, O, Franke, A, Rawlik, K, Ellinghaus, D, Hoischen, A, Schmidt, A, Ludwig, K |
| بيانات النشر: | Cell Press US |
| سنة النشر: | 2024 |
| المجموعة: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| مصطلحات موضوعية: | burden analysi, host genetic, immune deficiency, infection, innate immunity, rare variant, SARS-CoV-2, targeted sequencing, toll-like receptor 7, variant collapsing analysi |
| الوصف: | Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/38944683; info:eu-repo/semantics/altIdentifier/wos/WOS:001283966900001; volume:5; issue:4; journal:HGG ADVANCES; https://hdl.handle.net/10281/490505; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85199449450 |
| DOI: | 10.1016/j.xhgg.2024.100323 |
| الاتاحة: | https://hdl.handle.net/10281/490505 https://doi.org/10.1016/j.xhgg.2024.100323 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.A8FA84FC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.xhgg.2024.100323 |
|---|