{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:48:24Z","timestamp":1783529304739,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014098","name":"DNA Genotek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>COVID-19 disease has infected more than 772 million people, leading to 7 million deaths. Although the severe course of COVID-19 can be prevented using appropriate treatments, effective interventions require a thorough research of the genetic factors involved in its pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a genome-wide association study (GWAS) on 7,124 individuals (comprising 6,400 controls who had mild to moderate COVID-19 and 724 cases with severe COVID-19). The inclusion criteria were acute respiratory distress syndrome (ARDS), acute respiratory failure (ARF) requiring respiratory support, or CT scans indicative of severe COVID-19 infection without any competing diseases. We also developed a polygenic risk score (PRS) model to identify individuals at high risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified two genome-wide significant loci (<jats:italic>P<\/jats:italic>-value &amp;lt;5 \u00d7 10<jats:sup>\u22128<\/jats:sup>) and one locus with approximately genome-wide significance (<jats:italic>P<\/jats:italic>-value = 5.92 \u00d7 10<jats:sup>\u22128<\/jats:sup>-6.15 \u00d7 10<jats:sup>\u22128<\/jats:sup>). The most genome-wide significant variants were located in the <jats:italic>leucine zipper transcription factor like 1<\/jats:italic> (<jats:italic>LZTFL1<\/jats:italic>) gene, which has been highlighted in several previous GWAS studies. Our PRS model results indicated that individuals in the top 10% group of the PRS had twice the risk of severe course of the disease compared to those at median risk [odds ratio = 2.18 (1.66, 2.86), <jats:italic>P<\/jats:italic>-value = 8.9 \u00d7 10<jats:sup>\u22129<\/jats:sup>].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conducted one of the largest studies to date on the genetics of severe COVID-19 in an Eastern European cohort. Our results are consistent with previous research and will guide further epidemiologic studies on host genetics, as well as for the development of targeted treatments.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1409714","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T04:40:26Z","timestamp":1726720826000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["GWAS and polygenic risk score of severe COVID-19 in Eastern 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