{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:13:25Z","timestamp":1790694805516,"version":"4.1.0"},"reference-count":119,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Innovative Medicines Initiative 2 Joint Undertaking","award":["115976"],"award-info":[{"award-number":["115976"]}]},{"name":"European Union's Horizon 2020"},{"DOI":"10.13039\/100013322","name":"European Federation of Pharmaceutical Industries and Associations","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Agency","award":["00007\/COVI\/20"],"award-info":[{"award-number":["00007\/COVI\/20"]}]},{"name":"The University of Nottingham Group"},{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre"},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer\u2019s Society and ARUK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer\u2019s disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known.<\/jats:p>\n               <jats:p>Using genotyping from 1313 individuals with sporadic Alzheimer\u2019s disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer\u2019s disease. The same OAS1 locus has been recently associated with severe coronavirus disease 2019 (COVID-19) outcomes, linking risk for both diseases. The single nucleotide polymorphisms rs1131454(A) and rs4766676(T) are associated with Alzheimer\u2019s disease, and rs10735079(A) and rs6489867(T) are associated with severe COVID-19, where the risk alleles are linked with decreased OAS1 expression. Analysing single-cell RNA-sequencing data of myeloid cells from Alzheimer\u2019s disease and COVID-19 patients, we identify co-expression networks containing interferon (IFN)-responsive genes, including OAS1, which are significantly upregulated with age and both diseases. In human induced pluripotent stem cell-derived microglia with lowered OAS1 expression, we show exaggerated production of TNF-\u03b1 with IFN-\u03b3 stimulation, indicating OAS1 is required to limit the pro-inflammatory response of myeloid cells.<\/jats:p>\n               <jats:p>Collectively, our data support a link between genetic risk for Alzheimer\u2019s disease and susceptibility to critical illness with COVID-19 centred on OAS1, a finding with potential implications for future treatments of Alzheimer\u2019s disease and COVID-19, and development of biomarkers to track disease progression.<\/jats:p>","DOI":"10.1093\/brain\/awab337","type":"journal-article","created":{"date-parts":[[2021,9,11]],"date-time":"2021-09-11T19:09:58Z","timestamp":1631387398000},"page":"3727-3741","source":"Crossref","is-referenced-by-count":107,"title":["A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the <i>OAS1<\/i> gene"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1512-5474","authenticated-orcid":false,"given":"Naciye","family":"Magusali","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute at UCL, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-8705","authenticated-orcid":false,"given":"Andrew C","family":"Graham","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M","family":"Piers","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, Queen Square Institute of Neurology, UCL, London WC1N 1PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantila","family":"Panichnantakul","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, 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University Park, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eftychia","family":"Bellou","sequence":"additional","affiliation":[{"name":"Dementia Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5909-7391","authenticated-orcid":false,"given":"Sevinc","family":"Bayram","sequence":"additional","affiliation":[{"name":"Hitachi Rail Europe Ltd, New Ludgate, London EC4M 7HX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Sokolova","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Ryten","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases, Queen Square Institute of Neurology, UCL, London WC1N 1PJ, UK"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL, London WC1N 1EH, UK"},{"name":"Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, UCL, London WC1N 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-6449","authenticated-orcid":false,"given":"Carlo","family":"Sala Frigerio","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1784-5483","authenticated-orcid":false,"given":"Valentina","family":"Escott-Price","sequence":"additional","affiliation":[{"name":"Dementia Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, 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