{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:30:41Z","timestamp":1786494641408,"version":"build-2736575974"},"reference-count":44,"publisher":"The Royal Society","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation, Brasil","doi-asserted-by":"publisher","award":["05652-0\/2020"],"award-info":[{"award-number":["05652-0\/2020"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation, Brasil","doi-asserted-by":"publisher","award":["2024\/04362-9"],"award-info":[{"award-number":["2024\/04362-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation, Brasil","doi-asserted-by":"publisher","award":["2024\/03551-2"],"award-info":[{"award-number":["2024\/03551-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>COVID-19 and obesity are complex conditions marked by immune and metabolic dysfunction, with the former still ranking among the leading causes of death from infectious diseases worldwide and the latter reaching pandemic proportions. Clinical evidence consistently shows that obesity increases the risk of severe COVID-19, yet the biological mechanisms underlying this association remain unclear. Given their physiological and clinical overlap, they may share genetic pathways. We investigated genetic variants jointly associated with body mass index (BMI) and COVID-19 using publicly available genome-wide data. A conjunctional false discovery rate (conjFDR) approach identified shared variants between BMI and three COVID-19 phenotypes: infection, hospitalization and very severe respiratory illness. Functional annotation and pathway enrichment analyses were performed to explore the biological context of these variants, followed by a phenome-wide association study (PheWAS) to characterize pleiotropy. Shared variants were enriched in immune, metabolic and hormonal signaling pathways, including metal ion transport and glycosylation. The overlap with BMI was strongest for hospitalized and severe cases, suggesting common mechanisms underlying disease progression rather than infection. These findings suggest a biologically meaningful genetic overlap between obesity and COVID-19 severity, highlighting pleiotropy as a key feature in complex disease interactions and potential shared therapeutic targets.<\/jats:p>","DOI":"10.1098\/rsos.252355","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:15:30Z","timestamp":1786493730000},"source":"Crossref","is-referenced-by-count":0,"title":["Common genetic mechanisms between obesity and COVID-19 severity: unravelling pleiotropic loci and biological pathways"],"prefix":"10.1098","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7352-3935","authenticated-orcid":false,"given":"Giulia","family":"Souza da Costa","sequence":"first","affiliation":[{"name":"Graduate Program in Biosciences, Federal University of Health Sciences of Porto Alegre 1 , Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cibele E.","family":"Bandeira","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre 2 , Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Pereira Ciochetti","sequence":"additional","affiliation":[{"name":"University of S\u00e3o Paulo 5 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella F.","family":"Temoteo","sequence":"additional","affiliation":[{"name":"University of S\u00e3o Paulo 5 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Rodrigues Martinello","sequence":"additional","affiliation":[{"name":"Biomedicine School, Federal University of Health Sciences of Porto Alegre 3 , Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais","family":"Martins-Silva","sequence":"additional","affiliation":[{"name":"Federal University of Pelotas 6 , Pelotas, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raissa","family":"Nunes Dos Santos","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre 2 , Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego L.","family":"Rovaris","sequence":"additional","affiliation":[{"name":"University of S\u00e3o Paulo 5 , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilu","family":"Fiegenbaum","sequence":"additional","affiliation":[{"name":"Graduate Program in Biosciences, Federal University of Health Sciences of Porto Alegre 1 , Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Campos Pellanda","sequence":"additional","affiliation":[{"name":"Graduate Program in Pediatrics, Federal University of Health Sciences of Porto Alegre 4 , Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Tovo-Rodrigues","sequence":"additional","affiliation":[{"name":"Graduate Program in Epidemiology, Federal University of Pelotas 7 , Pelotas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia","family":"Pasqualini Genro","sequence":"additional","affiliation":[{"name":"Graduate Program in Biosciences, Federal University of Health Sciences of Porto Alegre 1 , Porto Alegre, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026081120144638500_RSOS252355C1","volume-title":"Health Statistics 2024: monitoring health for the SDGs, sustainable development goals","author":"World Health Organization","year":"2024"},{"key":"2026081120144638500_RSOS252355C2","article-title":"COVID-19 pandemic - our world in data","author":"Edouard","year":"2024"},{"key":"2026081120144638500_RSOS252355C3","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the chinese center for disease control and prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"2026081120144638500_RSOS252355C4","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/s41586-021-03767-x","article-title":"Mapping the human genetic architecture of COVID-19","volume":"600","author":"Niemi","year":"2021","journal-title":"Nature"},{"key":"2026081120144638500_RSOS252355C5","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.1038\/s41586-023-06355-3","article-title":"A second update on mapping the human genetic architecture of COVID-19","volume":"621","author":"Kanai","year":"2023","journal-title":"Nature"},{"key":"2026081120144638500_RSOS252355C6","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1038\/ijo.2008.247","article-title":"WHO recognition of the global obesity epidemic","volume":"32","author":"James","year":"2008","journal-title":"Int. J. Obes."},{"key":"2026081120144638500_RSOS252355C7","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0140-6736(23)02750-2","article-title":"Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults","volume":"403","author":"Phelps","year":"2024","journal-title":"Lancet"},{"key":"2026081120144638500_RSOS252355C8","doi-asserted-by":"crossref","first-page":"355","DOI":"10.15585\/mmwr.mm7010e4","article-title":"Body mass index and risk for COVID-19\u2013related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death","volume":"70","author":"Kompaniyets","year":"2021","journal-title":"MMWR Morb. Mortal. Wkly Rep."},{"key":"2026081120144638500_RSOS252355C9","doi-asserted-by":"crossref","first-page":"7212355","DOI":"10.1155\/2024\/7212355","article-title":"The role of obesity in the poor prognosis of COVID-19 infection: a review of 192 patients","volume":"2024","author":"Feghaly","year":"2024","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"2026081120144638500_RSOS252355C10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41577-020-0311-8","article-title":"The trinity of COVID-19: immunity, inflammation and intervention","volume":"20","author":"Tay","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"2026081120144638500_RSOS252355C11","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-020-03065-y","article-title":"Genetic mechanisms of critical illness in COVID-19","volume":"591","author":"Pairo-Castineira","year":"2020","journal-title":"Nature"},{"key":"2026081120144638500_RSOS252355C12","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1056\/NEJMoa2020283","article-title":"Genomewide association study of severe Covid-19 with respiratory failure","volume":"383","author":"The Severe Covid-19 GWAS Group","year":"2020","journal-title":"New Engl. J. Med."},{"key":"2026081120144638500_RSOS252355C13","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1093\/hmg\/ddy271","article-title":"Meta-analysis of genome-wide association studies for height and body mass index in \u223c700000 individuals of European ancestry","volume":"27","author":"Yengo","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"2026081120144638500_RSOS252355C14","doi-asserted-by":"crossref","first-page":"e1003553","DOI":"10.1371\/journal.pmed.1003553","article-title":"Cardiometabolic risk factors for COVID-19 susceptibility and severity: a Mendelian randomization analysis","volume":"18","author":"Leong","year":"2021","journal-title":"PLoS Med."},{"key":"2026081120144638500_RSOS252355C15","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1093\/ije\/dyac129","article-title":"The association of obesity-related traits on COVID-19 severity and hospitalization is affected by socio-economic status: a multivariable Mendelian randomization study","volume":"51","author":"Cabrera-Mendoza","year":"2022","journal-title":"Int. J. Epidemiol."},{"key":"2026081120144638500_RSOS252355C16","doi-asserted-by":"crossref","first-page":"154732","DOI":"10.1016\/j.metabol.2021.154732","article-title":"Impact of body composition on COVID-19 susceptibility and severity: a two-sample multivariable Mendelian randomization study","volume":"118","author":"Freuer","year":"2021","journal-title":"Metabolism"},{"key":"2026081120144638500_RSOS252355C17","doi-asserted-by":"crossref","first-page":"1325939","DOI":"10.3389\/fendo.2024.1325939","article-title":"Investigating the shared genetic architecture between COVID-19 and obesity: a large-scale genome wide cross-trait analysis","volume":"15","author":"Chen","year":"2024","journal-title":"Front. Endocrinol."},{"key":"2026081120144638500_RSOS252355C18","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00439-019-02060-2","article-title":"Discovery of shared genomic loci using the conditional false discovery rate approach","volume":"139","author":"Smeland","year":"2020","journal-title":"Hum. Genet."},{"key":"2026081120144638500_RSOS252355C19","doi-asserted-by":"crossref","first-page":"e1003455","DOI":"10.1371\/journal.pgen.1003455","article-title":"Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate","volume":"9","author":"Andreassen","year":"2013","journal-title":"PLoS Genet."},{"key":"2026081120144638500_RSOS252355C20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-14-S18-S1","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2026081120144638500_RSOS252355C21","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"EnrichR: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2026081120144638500_RSOS252355C22","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1002\/cpz1.90","article-title":"Gene set knowledge discovery with EnrichR","volume":"1","author":"Xie","year":"2021","journal-title":"Curr. Protoc."},{"key":"2026081120144638500_RSOS252355C23","doi-asserted-by":"crossref","first-page":"W185","DOI":"10.1093\/nar\/gkaa420","article-title":"SNPnexus: a web server for functional annotation of human genome sequence variation (2020 update)","volume":"48","author":"Oscanoa","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2026081120144638500_RSOS252355C24","doi-asserted-by":"crossref","first-page":"931313","DOI":"10.3389\/fnut.2022.931313","article-title":"Obesity and infection: what have we learned from the COVID-19 pandemic","volume":"9","author":"Vassilopoulou","year":"2022","journal-title":"Front. Nutr."},{"key":"2026081120144638500_RSOS252355C25","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41588-023-01384-0","article-title":"Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries","volume":"55","author":"Liu","year":"2023","journal-title":"Nat. Genet."},{"key":"2026081120144638500_RSOS252355C26","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41586-022-04434-5","article-title":"Mapping genomic loci implicates genes and synaptic biology in schizophrenia","volume":"604","author":"Trubetskoy","year":"2022","journal-title":"Nature"},{"key":"2026081120144638500_RSOS252355C27","doi-asserted-by":"crossref","first-page":"e140978","DOI":"10.1172\/jci.insight.140978","article-title":"Pleiotropic ZIP8 A391T implicates abnormal manganese homeostasis in complex human disease","volume":"5","author":"Sunuwar","year":"2020","journal-title":"JCI Insight"},{"key":"2026081120144638500_RSOS252355C28","doi-asserted-by":"crossref","first-page":"775591","DOI":"10.3389\/fgene.2021.775591","article-title":"Shared genetic architecture and causal relationship between asthma and cardiovascular diseases: a large-scale cross-trait analysis","volume":"12","author":"Zhou","year":"2022","journal-title":"Front. Genet."},{"key":"2026081120144638500_RSOS252355C29","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00439-011-1103-9","article-title":"Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE network","volume":"131","author":"Crosslin","year":"2011","journal-title":"Hum. Genet."},{"key":"2026081120144638500_RSOS252355C30","doi-asserted-by":"crossref","first-page":"e03718-21","DOI":"10.1128\/mbio.03718-21","article-title":"Inhibition of protein N-glycosylation blocks SARS-CoV-2 infection","volume":"13","author":"Casas-Sanchez","year":"2022","journal-title":"mBio"},{"key":"2026081120144638500_RSOS252355C31","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/ng.3528","article-title":"Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci","volume":"48","author":"Ellinghaus","year":"2016","journal-title":"Nat. Genet."},{"key":"2026081120144638500_RSOS252355C32","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41588-020-00757-z","article-title":"Genetics of 35 blood and urine biomarkers in the UK Biobank","volume":"53","author":"Sinnott-Armstrong","year":"2021","journal-title":"Nat. Genet."},{"key":"2026081120144638500_RSOS252355C33","doi-asserted-by":"crossref","first-page":"6939","DOI":"10.1038\/s41467-022-34688-6","article-title":"Pleiotropic genetic architecture and novel loci for C-reactive protein levels","volume":"13","author":"Koskeridis","year":"2022","journal-title":"Nat. Commun."},{"key":"2026081120144638500_RSOS252355C34","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.ajhg.2018.09.009","article-title":"Genome analyses of &gt;200,000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders","volume":"103","author":"Ligthart","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"2026081120144638500_RSOS252355C35","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1038\/s41467-022-29650-5","article-title":"Genetic analysis of over half a million people characterises C-reactive protein loci","volume":"13","author":"Said","year":"2022","journal-title":"Nat. Commun."},{"key":"2026081120144638500_RSOS252355C36","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.cell.2020.08.008","article-title":"The polygenic and monogenic basis of blood traits and diseases","volume":"182","author":"Vuckovic","year":"2020","journal-title":"Cell"},{"key":"2026081120144638500_RSOS252355C37","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1164\/rccm.201206-1013OC","article-title":"Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease","volume":"186","author":"Kim","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026081120144638500_RSOS252355C38","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41588-018-0321-7","article-title":"New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries","volume":"51","author":"Shrine","year":"2019","journal-title":"Nat. Genet."},{"key":"2026081120144638500_RSOS252355C39","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41581-020-00357-4","article-title":"Immunity, endothelial injury and complement-induced coagulopathy in COVID-19","volume":"17","author":"Perico","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"2026081120144638500_RSOS252355C40","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1093\/infdis\/jiaa349","article-title":"Elevated expression of serum endothelial cell adhesion molecules in COVID-19 patients","volume":"222","author":"Tong","year":"2020","journal-title":"J. Infect. Dis."},{"key":"2026081120144638500_RSOS252355C41","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"New Engl. J. Med."},{"key":"2026081120144638500_RSOS252355C42","doi-asserted-by":"crossref","first-page":"100751","DOI":"10.1016\/j.clinsp.2025.100751","article-title":"The complex architecture of COVID-19: clinical determinants and deepening of inequities as three epidemic waves progress","volume":"80","author":"Souza da Costa","year":"2025","journal-title":"Clinics"},{"key":"2026081120144638500_RSOS252355C43","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.stem.2020.11.009","article-title":"Androgen signaling regulates SARS-CoV-2 receptor levels and is associated with severe COVID-19 symptoms in men","volume":"27","author":"Samuel","year":"2020","journal-title":"Cell Stem Cell"},{"key":"2026081120144638500_RSOS252355C44","doi-asserted-by":"crossref","first-page":"624698","DOI":"10.3389\/fphys.2021.624698","article-title":"Metabolic alterations in SARS-CoV-2 infection and its implication in kidney dysfunction","volume":"12","author":"Andrade Silva","year":"2021","journal-title":"Front. Physiol."}],"container-title":["Royal Society Open Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/rsos\/article-pdf\/doi\/10.1098\/rsos.252355\/6156064\/rsos.252355.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/royalsocietypublishing.org\/rsos\/article-pdf\/doi\/10.1098\/rsos.252355\/6156064\/rsos.252355.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:15:36Z","timestamp":1786493736000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/rsos\/article\/13\/8\/rsos252355\/482739\/Common-genetic-mechanisms-between-obesity-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,12]]}},"URL":"https:\/\/doi.org\/10.1098\/rsos.252355","relation":{},"ISSN":["2054-5703"],"issn-type":[{"value":"2054-5703","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"article-number":"rsos252355"}}