{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T13:10:37Z","timestamp":1775308237221,"version":"3.50.1"},"reference-count":80,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Grant 206194"],"award-info":[{"award-number":["Grant 206194"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00011\/4"],"award-info":[{"award-number":["MC_UU_00011\/4"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Target"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,8,7]]},"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The virus SARS-CoV-2 can exploit biological vulnerabilities (e.g. host proteins) in susceptible hosts that predispose to the development of severe COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>To identify host proteins that may contribute to the risk of severe COVID-19, we undertook proteome-wide genetic colocalisation tests, and polygenic (pan) and cis-Mendelian randomisation analyses leveraging publicly available protein and COVID-19 datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Our analytic approach identified several known targets (e.g. ABO, OAS1), but also nominated new proteins such as soluble Fas (colocalisation probability &gt;0.9, p=1 \u00d7 10\n                      <jats:sup>-4<\/jats:sup>\n                      ), implicating Fas-mediated apoptosis as a potential target for COVID-19 risk. The polygenic (pan) and cis-Mendelian randomisation analyses showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The\n                      <jats:italic>ABO<\/jats:italic>\n                      signal is highly pleiotropic, and a look-up of proteins associated with the\n                      <jats:italic>ABO<\/jats:italic>\n                      signal revealed that the strongest association was with soluble CD209. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_00011\/4). JSh and GJW were funded by the Wellcome Trust Grant 206194. This research was funded in part by the Wellcome Trust [Grant 206194]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.69719","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T10:00:13Z","timestamp":1628848813000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.69719","source":"Crossref","is-referenced-by-count":31,"title":["A proteome-wide genetic investigation identifies several SARS-CoV-2-exploited host targets of clinical relevance"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2960-6017","authenticated-orcid":true,"given":"Mohd","family":"Anisul","sequence":"first","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus","place":["Cambridge, United Kingdom"]},{"name":"Open Targets, Wellcome Genome Campus","place":["Hinxton, United 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