{"id":9300,"date":"2020-12-14T07:07:06","date_gmt":"2020-12-14T07:07:06","guid":{"rendered":"https:\/\/www.rhesusnegative.net\/staynegative\/?p=9300"},"modified":"2020-12-14T10:36:34","modified_gmt":"2020-12-14T10:36:34","slug":"genetic-mechanisms-of-critical-illness-in-covid-19","status":"publish","type":"post","link":"https:\/\/www.rhesusnegative.net\/staynegative\/genetic-mechanisms-of-critical-illness-in-covid-19\/","title":{"rendered":"Genetic mechanisms of critical illness in Covid-19"},"content":{"rendered":"<div style=\"padding-bottom:20px; padding-top:10px;\" class=\"hupso-share-buttons\"><!-- Hupso Share Buttons - https:\/\/www.hupso.com\/share\/ --><a class=\"hupso_toolbar\" href=\"https:\/\/www.hupso.com\/share\/\"><img data-recalc-dims=\"1\" decoding=\"async\" src=\"https:\/\/i0.wp.com\/static.hupso.com\/share\/buttons\/share-medium.png?w=640&#038;ssl=1\" style=\"border:0px; padding-top:5px; float:left;\" alt=\"Share Button\"\/><\/a><script type=\"text\/javascript\">var hupso_services_t=new Array(\"Twitter\",\"Facebook\",\"Pinterest\",\"Linkedin\");var hupso_background_t=\"#EAF4FF\";var hupso_border_t=\"#66CCFF\";var hupso_toolbar_size_t=\"medium\";var hupso_twitter_via = \"datebytype\";var hupso_image_folder_url = \"\";var hupso_twitter_via=\"datebytype\";var hupso_url_t=\"\";var hupso_title_t=\"Genetic mechanisms of critical illness in Covid-19\";<\/script><script type=\"text\/javascript\" src=\"https:\/\/static.hupso.com\/share\/js\/share_toolbar.js\"><\/script><!-- Hupso Share Buttons --><\/div>\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\"><p>The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs[PMID: 32526193] and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases.[PMID: 32678530] Since susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable traits, we reasoned that host genetic variation may identify mechanistic targets for therapeutic development in Covid-19.[PMID: 24855243] GenOMICC (Genetics Of Mortality In Critical Care, &lt;a href=&#8221;https:\/\/genomicc.org&#8221;><a href=\"https:\/\/genomicc.org\" target=\"_blank\" rel=\"noreferrer noopener\" aria-label=\"genomicc.org (opens in a new tab)\">genomicc.org<\/a>&lt;\/a>) is a global collaborative study to understand the genetic basis of critical illness. Here we report the results of a genome-wide association study (GWAS) in 2244 critically-ill Covid-19 patients from 208 UK intensive care units (ICUs), representing >95% of all ICU beds. Ancestry-matched controls were drawn from the UK Biobank population study and results were confirmed in GWAS comparisons with two other population control groups: the 100,000 genomes project and Generation Scotland. We identify and replicate three novel genome-wide significant associations, at chr19p13.3 (rs2109069, p = 3.98 x 10<sup>-12<\/sup>), within the gene encoding dipeptidyl peptidase 9 (DPP9), at chr12q24.13 (rs10735079, p = 1.65 x 10<sup>-8<\/sup>) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), and at chr21q22.1 (rs2236757, p = 4.99 x 10<sup>-8<\/sup>) in the interferon receptor gene IFNAR2. Consistent with our focus on extreme disease in younger patients with less comorbidity, we detect a stronger signal at the known 3p21.31 locus than previous studies (rs73064425, p = 4.77 x 10<sup>-30<\/sup>).<br><\/p><cite><a href=\"https:\/\/www.medrxiv.org\/content\/10.1101\/2020.09.24.20200048v2?fbclid=IwAR16Vg9jhwkNp2Inml4Oeq-Yix3lo3X_Z1hUu1SWhU5nC1cw0a1guBzlOd0\" target=\"_blank\" rel=\"noreferrer noopener\" aria-label=\"https:\/\/www.medrxiv.org\/content\/10.1101\/2020.09.24.20200048v2?fbclid=IwAR16Vg9jhwkNp2Inml4Oeq-Yix3lo3X_Z1hUu1SWhU5nC1cw0a1guBzlOd0 (opens in a new tab)\">https:\/\/www.medrxiv.org\/content\/10.1101\/2020.09.24.20200048v2?fbclid=IwAR16Vg9jhwkNp2Inml4Oeq-Yix3lo3X_Z1hUu1SWhU5nC1cw0a1guBzlOd0<\/a><\/cite><\/blockquote>\n<div style=\"padding-bottom:20px; padding-top:10px;\" class=\"hupso-share-buttons\"><!-- Hupso Share Buttons - https:\/\/www.hupso.com\/share\/ --><a class=\"hupso_toolbar\" href=\"https:\/\/www.hupso.com\/share\/\"><img data-recalc-dims=\"1\" decoding=\"async\" src=\"https:\/\/i0.wp.com\/static.hupso.com\/share\/buttons\/share-medium.png?w=640&#038;ssl=1\" style=\"border:0px; padding-top:5px; float:left;\" alt=\"Share Button\"\/><\/a><script type=\"text\/javascript\">var hupso_services_t=new Array(\"Twitter\",\"Facebook\",\"Pinterest\",\"Linkedin\");var hupso_background_t=\"#EAF4FF\";var hupso_border_t=\"#66CCFF\";var hupso_toolbar_size_t=\"medium\";var hupso_twitter_via = \"datebytype\";var hupso_image_folder_url = \"\";var hupso_twitter_via=\"datebytype\";var hupso_url_t=\"\";var hupso_title_t=\"Genetic mechanisms of critical illness in Covid-19\";<\/script><script type=\"text\/javascript\" src=\"https:\/\/static.hupso.com\/share\/js\/share_toolbar.js\"><\/script><!-- Hupso Share Buttons --><\/div>","protected":false},"excerpt":{"rendered":"<div style=\"padding-bottom:20px; padding-top:10px;\" class=\"hupso-share-buttons\"><!-- Hupso Share Buttons - https:\/\/www.hupso.com\/share\/ --><a class=\"hupso_toolbar\" href=\"https:\/\/www.hupso.com\/share\/\"><img src=\"https:\/\/static.hupso.com\/share\/buttons\/share-medium.png\" style=\"border:0px; padding-top:5px; float:left;\" alt=\"Share Button\"\/><\/a><script type=\"text\/javascript\">var hupso_services_t=new Array(\"Twitter\",\"Facebook\",\"Pinterest\",\"Linkedin\");var hupso_background_t=\"#EAF4FF\";var hupso_border_t=\"#66CCFF\";var hupso_toolbar_size_t=\"medium\";var hupso_twitter_via = \"datebytype\";var hupso_image_folder_url = \"\";var hupso_twitter_via=\"datebytype\";var hupso_url_t=\"\";var hupso_title_t=\"Genetic mechanisms of critical illness in Covid-19\";<\/script><script type=\"text\/javascript\" src=\"https:\/\/static.hupso.com\/share\/js\/share_toolbar.js\"><\/script><!-- Hupso Share Buttons --><\/div>The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases. Since susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable traits, we reasoned that host genetic variation may identify mechanistic targets for therapeutic development in Covid-19. GenOMICC (Genetics Of Mortality In Critical Care, &lt;a href=&#8221;https:\/\/genomicc.org&#8221;>genomicc.org&lt;\/a>) is a global collaborative study to understand the genetic basis of critical illness. Here we report the results of a genome-wide association study (GWAS) in 2244 critically-ill Covid-19 patients from 208 UK intensive care units (ICUs), representing >95% of all ICU beds. Ancestry-matched controls were drawn <div style=\"padding-bottom:20px; padding-top:10px;\" class=\"hupso-share-buttons\"><!-- Hupso Share Buttons - https:\/\/www.hupso.com\/share\/ --><a class=\"hupso_toolbar\" href=\"https:\/\/www.hupso.com\/share\/\"><img src=\"https:\/\/static.hupso.com\/share\/buttons\/share-medium.png\" style=\"border:0px; padding-top:5px; float:left;\" alt=\"Share Button\"\/><\/a><script type=\"text\/javascript\">var hupso_services_t=new Array(\"Twitter\",\"Facebook\",\"Pinterest\",\"Linkedin\");var hupso_background_t=\"#EAF4FF\";var hupso_border_t=\"#66CCFF\";var hupso_toolbar_size_t=\"medium\";var hupso_twitter_via = \"datebytype\";var hupso_image_folder_url = \"\";var hupso_twitter_via=\"datebytype\";var hupso_url_t=\"\";var hupso_title_t=\"Genetic mechanisms of critical illness in Covid-19\";<\/script><script type=\"text\/javascript\" src=\"https:\/\/static.hupso.com\/share\/js\/share_toolbar.js\"><\/script><!-- Hupso Share Buttons --><\/div>","protected":false},"author":1,"featured_media":8520,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"amp_status":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","enabled":false},"version":2}},"categories":[1],"tags":[],"class_list":["post-9300","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-facts"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/www.rhesusnegative.net\/staynegative\/wp-content\/uploads\/2020\/08\/image-4.jpg?fit=674%2C379&ssl=1","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p5DV68-2q0","_links":{"self":[{"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/posts\/9300","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/comments?post=9300"}],"version-history":[{"count":3,"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/posts\/9300\/revisions"}],"predecessor-version":[{"id":9321,"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/posts\/9300\/revisions\/9321"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/media\/8520"}],"wp:attachment":[{"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/media?parent=9300"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/categories?post=9300"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rhesusnegative.net\/staynegative\/wp-json\/wp\/v2\/tags?post=9300"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}