{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:45:08Z","timestamp":1784760308437,"version":"3.55.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["COV20_00622"],"award-info":[{"award-number":["COV20_00622"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["COV20\/00792"],"award-info":[{"award-number":["COV20\/00792"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["COV20_00181"],"award-info":[{"award-number":["COV20_00181"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["COV20_1144"],"award-info":[{"award-number":["COV20_1144"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00876"],"award-info":[{"award-number":["PI20\/00876"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Obra Social La Caixa"},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["RTC-2017-6471-1"],"award-info":[{"award-number":["RTC-2017-6471-1"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cabildo Insular de Tenerife","award":["CGIEU0000219140"],"award-info":[{"award-number":["CGIEU0000219140"]}]},{"name":"Fundaci\u00f3n Canaria Instituto de Investigaci\u00f3n Sanitaria de Canarias","award":["PIFIISC20\/57"],"award-info":[{"award-number":["PIFIISC20\/57"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Here, we describe the results of a genome-wide study conducted in 11\u2009939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P\u2009&amp;lt;\u20095\u2009\u00d7\u200910\u22128) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P\u2009=\u00a01.3\u2009\u00d7\u200910\u221222 and P\u2009=\u00a08.1\u2009\u00d7\u200910\u221212, respectively), and for variants in 9q21.32 near TLE1 only among females (P\u2009=\u00a04.4\u2009\u00d7\u200910\u22128). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P\u2009=\u00a02.7\u2009\u00d7\u200910\u22128) and ARHGAP33 (P\u2009=\u00a01.3\u2009\u00d7\u200910\u22128), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P\u2009=\u20094.1\u2009\u00d7\u200910\u22128). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (&amp;lt;60 or \u226560\u00a0years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.<\/jats:p>","DOI":"10.1093\/hmg\/ddac132","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T14:05:01Z","timestamp":1655388301000},"page":"3789-3806","source":"Crossref","is-referenced-by-count":62,"title":["Novel genes and sex differences in COVID-19 severity"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6964-8898","authenticated-orcid":false,"given":"Raquel","family":"Cruz","sequence":"first","affiliation":[{"name":"Centro Nacional de Genotipado (CEGEN), Universidade de Santiago de Compostela , 15706 Santiago de Compostela, Spain"},{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III , 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS) , 15706 Santiago de Compostela, Spain"},{"name":"Centro Singular de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas (CIMUS), Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Diz-de Almeida","sequence":"additional","affiliation":[{"name":"Centro Singular de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas (CIMUS), Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"L\u00f3pez de Heredia","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III , 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Quintela","sequence":"additional","affiliation":[{"name":"Centro Nacional de Genotipado (CEGEN), Universidade de Santiago de Compostela , 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco C","family":"Ceballos","sequence":"additional","affiliation":[{"name":"Unidad de Infecci\u00f3n Viral e Inmunidad , Centro Nacional de Microbiolog\u00eda (CNM), , 28220 Madrid, Spain"},{"name":"Instituto de Salud Carlos III (ISCIII) , Centro Nacional de Microbiolog\u00eda (CNM), , 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Pita","sequence":"additional","affiliation":[{"name":"Spanish National Cancer Research Centre, Human Genotyping-CEGEN Unit , 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M","family":"Lorenzo-Salazar","sequence":"additional","affiliation":[{"name":"Genomics Division, Instituto Tecnol\u00f3gico y de Energ\u00edas Renovables , 38600 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Gonz\u00e1lez-Montelongo","sequence":"additional","affiliation":[{"name":"Genomics Division, Instituto Tecnol\u00f3gico y de Energ\u00edas Renovables , 38600 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Gago-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n P\u00fablica Galega de Medicina Xen\u00f3mica, Sistema Galego de Sa\u00fade (SERGAS) , 15706 Santiago de Compostela, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS) , 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sevilla Porras","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III , 28029 Madrid, Spain"},{"name":"Instituto de Gen\u00e9tica M\u00e9dica y 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