{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:11:23Z","timestamp":1789164683862,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003086","name":"Basque Government Health Department","doi-asserted-by":"publisher","award":["2020333038"],"award-info":[{"award-number":["2020333038"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003086","name":"Basque Government Health Department","doi-asserted-by":"publisher","award":["RD21\/0002\/0056"],"award-info":[{"award-number":["RD21\/0002\/0056"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003086","name":"Basque Government Health Department","doi-asserted-by":"publisher","award":["BIDP-III-2018-12"],"award-info":[{"award-number":["BIDP-III-2018-12"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["2020333038"],"award-info":[{"award-number":["2020333038"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["RD21\/0002\/0056"],"award-info":[{"award-number":["RD21\/0002\/0056"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["BIDP-III-2018-12"],"award-info":[{"award-number":["BIDP-III-2018-12"]}]},{"name":"European Union\u2014NextGenerationEU, Mecanismo para la Recuperaci\u00f3n y la Resiliencia (MRR)","award":["2020333038"],"award-info":[{"award-number":["2020333038"]}]},{"name":"European Union\u2014NextGenerationEU, Mecanismo para la Recuperaci\u00f3n y la Resiliencia (MRR)","award":["RD21\/0002\/0056"],"award-info":[{"award-number":["RD21\/0002\/0056"]}]},{"name":"European Union\u2014NextGenerationEU, Mecanismo para la Recuperaci\u00f3n y la Resiliencia (MRR)","award":["BIDP-III-2018-12"],"award-info":[{"award-number":["BIDP-III-2018-12"]}]},{"name":"Secretar\u00eda Nacional de Ciencia y Tecnolog\u00eda e Innovaci\u00f3n","award":["2020333038"],"award-info":[{"award-number":["2020333038"]}]},{"name":"Secretar\u00eda Nacional de Ciencia y Tecnolog\u00eda e Innovaci\u00f3n","award":["RD21\/0002\/0056"],"award-info":[{"award-number":["RD21\/0002\/0056"]}]},{"name":"Secretar\u00eda Nacional de Ciencia y Tecnolog\u00eda e Innovaci\u00f3n","award":["BIDP-III-2018-12"],"award-info":[{"award-number":["BIDP-III-2018-12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The COVID-19 pandemic has had a devastating impact, with more than 7 million deaths worldwide. Advanced age and comorbidities partially explain severe cases of the disease, but genetic factors also play a significant role. Genome-wide association studies (GWASs) have been instrumental in identifying loci associated with SARS-CoV-2 infection. Here, we report the results from a &gt;820 K variant GWAS in a COVID-19 patient cohort from the hospitals associated with IIS Biobizkaia. We compared intensive care unit (ICU)-hospitalized patients with non-ICU-hospitalized patients. The GWAS was complemented with an integrated phenotype and genetic modeling analysis using HLA genotypes, a previously identified COVID-19 polygenic risk score (PRS) and clinical data. We identified four variants associated with COVID-19 severity with genome-wide significance (rs58027632 in KIF19; rs736962 in HTRA1; rs77927946 in DMBT1; and rs115020813 in LINC01283). In addition, we designed a multivariate predictive model including HLA, PRS and clinical data which displayed an area under the curve (AUC) value of 0.79. Our results combining human genetic information with clinical data may help to improve risk assessment for the development of a severe outcome of COVID-19.<\/jats:p>","DOI":"10.3390\/biom15030393","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T08:46:41Z","timestamp":1741596401000},"page":"393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Analysis and Predictive Modeling of COVID-19 Severity in a Hospital-Based Patient Cohort"],"prefix":"10.3390","volume":"15","author":[{"given":"Iraide","family":"Alloza-Moral","sequence":"first","affiliation":[{"name":"Inflammation & Biomarkers Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Physiology Department, Faculty of Medicine and Nursery, Basque Country University (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Red de Enfermedades Inflamatorias (REI), Redes de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS), Carlos IIII Health Research Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ane","family":"Aldekoa-Etxabe","sequence":"additional","affiliation":[{"name":"Inflammation & Biomarkers Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Red de Enfermedades Inflamatorias (REI), Redes de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS), Carlos IIII Health Research Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Tulloch-Navarro","sequence":"additional","affiliation":[{"name":"Inflammation & Biomarkers Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Red de Enfermedades Inflamatorias (REI), Redes de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS), Carlos IIII Health Research Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainhoa","family":"Fiat-Arriola","sequence":"additional","affiliation":[{"name":"Inflammation & Biomarkers Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Red de Enfermedades Inflamatorias (REI), Redes de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS), Carlos IIII Health Research Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mar","sequence":"additional","affiliation":[{"name":"Pneumology Department, Galdakao-Usansolo University Hospital, Biobizkaia Health Research Institute, 48960 Galdakao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9610-7392","authenticated-orcid":false,"given":"Eloisa","family":"Urrechaga","sequence":"additional","affiliation":[{"name":"Pneumology Department, Galdakao-Usansolo University Hospital, Biobizkaia Health Research Institute, 48960 Galdakao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8940-9053","authenticated-orcid":false,"given":"Cristina","family":"Ponga","sequence":"additional","affiliation":[{"name":"Pneumology Department, Galdakao-Usansolo University Hospital, Biobizkaia Health Research Institute, 48960 Galdakao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Artiga-Folch","sequence":"additional","affiliation":[{"name":"Inflammation & Biomarkers Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiara","family":"Garcia-Bediaga","sequence":"additional","affiliation":[{"name":"Bioinformatic Unit, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Aspichueta","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Medicine and Nursery, Basque Country University (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Research Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), 28029 Madrid, Spain"},{"name":"Biobizkaia Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4087-8729","authenticated-orcid":false,"given":"Cesar","family":"Martin","sequence":"additional","affiliation":[{"name":"Inflammation & Biomarkers Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Biochemistry and Molecular Biology Department, Science and Technology School, Basque Country University (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Biofisika Institute (UPV\/EHU, CSIC), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9815-2779","authenticated-orcid":false,"given":"Aitor","family":"Zarandona-Garai","sequence":"additional","affiliation":[{"name":"Bioinformatic Unit, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"P\u00e9rez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Bioinformatic Unit, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunate","family":"Arana-Arri","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Unit, Biobizkaia Health Research Institute, Cruces University Hospital, Plaza de Cruces s\/n, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6752-8000","authenticated-orcid":false,"given":"Juan-Carlos","family":"Trivi\u00f1o","sequence":"additional","affiliation":[{"name":"Bioinformatics Department, Sistemas Gen\u00f3micos, 46980 Peterna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ane","family":"Uranga","sequence":"additional","affiliation":[{"name":"Pneumology Department, Galdakao-Usansolo University Hospital, Biobizkaia Health Research Institute, 48960 Galdakao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro-Pablo","family":"Espa\u00f1a","sequence":"additional","affiliation":[{"name":"Pneumology Department, Galdakao-Usansolo University Hospital, Biobizkaia Health Research Institute, 48960 Galdakao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6967-6485","authenticated-orcid":false,"given":"Koen","family":"Vandenbroeck-van-Caeckenbergh","sequence":"additional","affiliation":[{"name":"Inflammation & Biomarkers Group, Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"Red de Enfermedades Inflamatorias (REI), Redes de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS), Carlos IIII Health Research Institute, 28029 Madrid, Spain"},{"name":"Biochemistry and Molecular Biology Department, Science and Technology School, Basque Country University (UPV\/EHU), 48940 Leioa, Spain"},{"name":"Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S0140-6736(20)30185-9","article-title":"A novel coronavirus outbreak of global health concern","volume":"395","author":"Wang","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. 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