{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:43:28Z","timestamp":1774485808104,"version":"3.50.1"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Operational Programme for Competitiveness and Internationalization","award":["POCI-01-0145-FEDER-028806"],"award-info":[{"award-number":["POCI-01-0145-FEDER-028806"]}]},{"name":"Operational Programme for Competitiveness and Internationalization","award":["POCI-01-0145-FEDER-016428"],"award-info":[{"award-number":["POCI-01-0145-FEDER-016428"]}]},{"name":"Operational Programme for Competitiveness and Internationalization","award":["CENTRO \u2013 46-2016-02"],"award-info":[{"award-number":["CENTRO \u2013 46-2016-02"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","award":["PTDC\/DTP-PIC\/2284\/2014"],"award-info":[{"award-number":["PTDC\/DTP-PIC\/2284\/2014"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","award":["PTDC\/BIA-MIC\/31849\/2017"],"award-info":[{"award-number":["PTDC\/BIA-MIC\/31849\/2017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","award":["UIDP\/04501\/2020"],"award-info":[{"award-number":["UIDP\/04501\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","award":["UI\/BD\/151337\/2021"],"award-info":[{"award-number":["UI\/BD\/151337\/2021"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Populations seem to respond differently to the global pandemic of severe acute respiratory syndrome coronavirus 2. Recent studies show individual variability in both susceptibility and clinical response to COVID-19 infection. People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups, being already associated with a poor prognosis upon infection. This study aims contributing to unveil the underlying reasons for such prognosis in people with COPD and the variability in the response observed across worldwide populations, by looking at the genetic background as a possible answer to COVID-19 infection response heterogeneity.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>SNPs already associated with susceptibility to COVID-19 infection (rs286914 and rs12329760) and severe COVID-19 with respiratory failure (rs657152 and rs11385942) were assessed and their allelic frequencies used to calculate the probability of having multiple risk alleles. This was performed on a Portuguese case-control COPD cohort, previously clinically characterized and genotyped from saliva samples, and also on worldwide populations (European, Spanish, Italian, African, American and Asian), using publicly available frequencies data. A polygenic risk analysis was also conducted on the Portuguese COPD cohort for the two mentioned phenotypes, and also for hospitalization and survival to COVID-19 infection.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Findings<\/jats:title><jats:p>No differences in genetic risk for COVID-19 susceptibility, hospitalization, severity or survival were found between people with COPD and the control group (all p-values &gt; 0.01), either considering risk alleles individually, allelic combinations or polygenic risk scores. All populations, even those with European ancestry (Portuguese, Spanish and Italian), showed significant differences from the European population in genetic risk for both COVID-19 susceptibility and severity (all p-values &lt; 0.0001).<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate a low genetic contribution for COVID-19 infection predisposition or worse outcomes observed in people with COPD. Also, our study unveiled a high genetic heterogeneity across major world populations for the same alleles, even within European sub-populations, demonstrating the need to build a higher resolution European genetic map, so that differences in the distribution of relevant alleles can be easily accessed and used to better manage diseases, ultimately, safeguarding populations with higher genetic predisposition to such diseases.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0264009","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T18:40:11Z","timestamp":1645641611000},"page":"e0264009","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Evaluation of the genetic risk for COVID-19 outcomes in COPD and differences among worldwide populations"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0699-335X","authenticated-orcid":true,"given":"Rui","family":"Mar\u00e7alo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonya","family":"Neto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Pinheiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana J.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuno","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel A. 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american college of academic international medicine-world academic council of emergency medicine multidisciplinary COVID-19 working group consensus paper","author":"S Stawicki","year":"2020","journal-title":"Journal of Global Infectious Diseases"},{"issue":"6","key":"pone.0264009.ref002","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41431-020-0636-6","article-title":"The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic","volume":"28","year":"2020","journal-title":"Eur J Hum Genet"},{"key":"pone.0264009.ref003","article-title":"Genomewide Association Study of Severe Covid-19 with Respiratory Failure","author":"D Ellinghaus","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0264009.ref004","article-title":"The landscape of host genetic factors involved in infection to common viruses and SARS-CoV-2","author":"L Kachuri","year":"2020","journal-title":"medRxiv Prepr Serv Heal Sci"},{"key":"pone.0264009.ref005","article-title":"New insights into genetic susceptibility of COVID-19: An ACE2 and TMPRSS2 polymorphism analysis","author":"Y Hou","year":"2020","journal-title":"BMC Med"},{"key":"pone.0264009.ref006","first-page":"446","volume-title":"Mayo Clinic Proceedings","author":"NL Pereira","year":"2021"},{"key":"pone.0264009.ref007","volume-title":"World health statistics 2018: monitoring health for the SDGs, sustainable development goals","year":"2018"},{"key":"pone.0264009.ref008","first-page":"26","article-title":"SARS-CoV-2 infection in the COPD population is associated with increased healthcare utilization: An analysis of Cleveland clinic\u2019s COVID-19 registry","author":"AA Attaway","year":"2020","journal-title":"EClinicalMedicine"},{"key":"pone.0264009.ref009","first-page":"2002108","volume-title":"European Respiratory Journal","author":"JM Leung","year":"2020"},{"key":"pone.0264009.ref010","author":"Centers for Disease Control and Prevention (CDC)","journal-title":"People with Certain Medical Conditions"},{"key":"pone.0264009.ref011","author":"Global Initiative for Chronic Obstructive Lung Disease","year":"2019","journal-title":"Global strategy for the diagnosis management and prevention of chronic obstructive pulmonary disease (2019 Report)"},{"key":"pone.0264009.ref012","author":"World Health Organization\u2014WHO","year":"1948","journal-title":"Preamble to the Constitution of the World Health Organization as adopted by the International Health Conference, New York, 19\u201322 June, 1946"},{"issue":"5","key":"pone.0264009.ref013","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1007\/s11357-012-9482-y","article-title":"Mood is a key determinant of cognitive performance in community-dwelling older adults: a cross-sectional analysis","volume":"35","author":"NC Santos","year":"2013","journal-title":"Age (Omaha)"},{"issue":"FEB","key":"pone.0264009.ref014","article-title":"Clinical, physical and lifestyle variables and relationship with cognition and mood in aging: A cross-sectional analysis of distinct educational groups","volume":"6","author":"NC Santos","year":"2014","journal-title":"Front Aging Neurosci"},{"issue":"3","key":"pone.0264009.ref015","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"2","key":"pone.0264009.ref016","doi-asserted-by":"crossref","DOI":"10.1002\/mpr.1608","article-title":"A tutorial on conducting genome-wide association studies: Quality control and statistical analysis","volume":"27","author":"AT Marees","year":"2018","journal-title":"Int J Methods Psychiatr 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Naj","year":"2019","journal-title":"Curr Protoc Hum Genet [Internet]"},{"issue":"8","key":"pone.0264009.ref021","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1002\/gepi.20533","article-title":"MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes","volume":"34","author":"Y Li","year":"2010","journal-title":"Genet Epidemiol"},{"issue":"7809","key":"pone.0264009.ref022","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"KJ Karczewski","year":"2020","journal-title":"Nature"},{"key":"pone.0264009.ref023","article-title":"ALFA: Allele Frequency Aggregator","author":"L. Phan","year":"2010","journal-title":"U.S. National Library of Medicine"},{"key":"pone.0264009.ref024","author":"NATIONAL HEART, LUNG ABI","journal-title":"GRASP: Genome-Wide Repository of Associations Between SNPs and Phenotypes"},{"issue":"9","key":"pone.0264009.ref025","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1093\/bioinformatics\/btu848","article-title":"PRSice: Polygenic Risk Score software","volume":"31","author":"J Euesden","year":"2015","journal-title":"Bioinformatics"},{"key":"pone.0264009.ref026","article-title":"Tutorial: a guide to performing polygenic risk score analyses","author":"SW Choi","year":"2020","journal-title":"Nature Protocols"},{"key":"pone.0264009.ref027","article-title":"A guide to performing Polygenic Risk Score analyses","author":"SW Choi","year":"2018","journal-title":"bioRxiv"},{"key":"pone.0264009.ref028","first-page":"20","article-title":"Chi-Square Test is Statistically Significant: Now What?","author":"D. Sharpe","year":"2015","journal-title":"Pract Assessment, Res Eval Pract Assess"},{"key":"pone.0264009.ref029","first-page":"49","volume-title":"Journal of Cellular Physiology","author":"S Mohammadpour","year":"2021"},{"issue":"23","key":"pone.0264009.ref030","doi-asserted-by":"crossref","first-page":"10007","DOI":"10.1021\/acs.jpclett.0c02765","article-title":"Decoding Asymptomatic COVID-19 Infection and Transmission","volume":"11","author":"R Wang","year":"2020","journal-title":"J Phys Chem Lett"},{"key":"pone.0264009.ref031","first-page":"3996","volume-title":"ACS Chemical Neuroscience.","author":"R. Lawaczeck","year":"2020"},{"key":"pone.0264009.ref032","first-page":"1541","volume-title":"Clinical Science.","author":"PJ Barnes","year":"2017"},{"key":"pone.0264009.ref033","first-page":"221","volume-title":"Autophagy","author":"AC Racanelli","year":"2018"},{"key":"pone.0264009.ref034","first-page":"3813","volume-title":"International Journal of COPD.","author":"Y Cui","year":"2018"},{"key":"pone.0264009.ref035","first-page":"1545","volume-title":"Journal of General Internal Medicine.","author":"F Jiang","year":"2020"},{"key":"pone.0264009.ref036","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/cjn.2021.148","article-title":"COVID-19 and its Cardiac and Neurological Complications among Ontario Visible Minorities","author":"JY Chu","year":"2021","journal-title":"Can J Neurol Sci"},{"issue":"5","key":"pone.0264009.ref037","doi-asserted-by":"crossref","first-page":"e2122","DOI":"10.1002\/rmv.2122","article-title":"Angiotensin-converting enzyme 2: The old door for new severe acute respiratory syndrome coronavirus 2 infection","volume":"30","author":"HW Tan","year":"2020","journal-title":"Rev Med Virol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:12:46Z","timestamp":1700266366000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264009"}},"subtitle":[],"editor":[{"given":"Yan-Ming","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0264009","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,23]]}}}