{"id":135,"date":"2025-01-30T19:23:43","date_gmt":"2025-01-30T19:23:43","guid":{"rendered":"https:\/\/mrivas.su.domains\/gbe\/?p=135"},"modified":"2025-02-24T17:33:31","modified_gmt":"2025-02-24T17:33:31","slug":"generating-effective-therapeutic-hypotheses-from-human-genetic-data","status":"publish","type":"post","link":"https:\/\/mrivas.su.domains\/gbe\/uncategorized\/generating-effective-therapeutic-hypotheses-from-human-genetic-data\/","title":{"rendered":"Generating effective therapeutic hypotheses from human genetic data"},"content":{"rendered":"\n<p><strong>Protective genetic mutations<\/strong> are a guide from natural experiments of Nature to identify genetically validated therapeutic targets.<br><br><a href=\"https:\/\/journals.plos.org\/plosgenetics\/article?id=10.1371\/journal.pgen.1008682\">For glaucoma<\/a>, we discovered loss-of-function variants in <em><strong>ANGPTL7<\/strong> <\/em>that <strong>lower intraocular pressure <\/strong>and <strong>protect against glaucoma<\/strong>. <a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.2020.368.6494.twil\"><em>Editor&#8217;s pick from Science<\/em> <em>journal<\/em>.<\/a><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"538\" src=\"https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-44-1024x538.png\" alt=\"\" class=\"wp-image-136\" srcset=\"https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-44-1024x538.png 1024w, https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-44-300x158.png 300w, https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-44-768x403.png 768w, https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-44.png 1200w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/figure>\n\n\n\n<p><br><a href=\"https:\/\/www.nature.com\/articles\/ng.952\">For Inflammatory Bowel Diseases<\/a>, we discovered loss-of-function variants in <strong><em><a href=\"https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC3378381\/\">CARD9<\/a><\/em><\/strong> and <em><strong><a href=\"https:\/\/www.nature.com\/articles\/ncomms12342\">RNF186<\/a> <\/strong><\/em>that <strong>protect against Crohn&#8217;s disease and <a href=\"https:\/\/www.broadinstitute.org\/news\/better-without-it-broken-gene-may-help-protect-against-ulcerative-colitis\">ulcerative colitis<\/a>. <\/strong><br><\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"800\" height=\"596\" src=\"https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-45.png\" alt=\"\" class=\"wp-image-137\" srcset=\"https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-45.png 800w, https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-45-300x224.png 300w, https:\/\/mrivas.su.domains\/gbe\/wp-content\/uploads\/2025\/01\/image-45-768x572.png 768w\" sizes=\"auto, (max-width: 800px) 100vw, 800px\" \/><\/figure>\n\n\n\n<p><br>For cancers, we discovered a missense variant in <em><strong>WNT6 <\/strong><\/em>that <strong><a href=\"https:\/\/mvp-ukbb.finngen.fi\/variant\/2-218871647-C-G\">protects against human cancers<\/a><\/strong>.<\/p>\n\n\n\n<p>For chronic kidney disease and its related biomarkers including creatinine and eGFR we discovered genetic variants that lowered Creatinine (improved eGFR) and <strong><a href=\"https:\/\/www.nature.com\/articles\/s41581-021-00400-y\">protected against chronic kidney disease<\/a><\/strong>. <\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" src=\"https:\/\/media.springernature.com\/lw1200\/springer-static\/image\/art%3A10.1038%2Fs41588-020-00757-z\/MediaObjects\/41588_2020_757_Fig2_HTML.png\" alt=\"\"\/><\/figure>\n\n\n\n<p>These are genetically validated therapeutic hypotheses that will hopefully lead to effective therapies.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Protective genetic mutations are a guide from natural experiments of Nature to identify genetically validated therapeutic targets. For glaucoma, we discovered loss-of-function variants in ANGPTL7 that lower intraocular pressure and protect against glaucoma. Editor&#8217;s pick from Science journal. For Inflammatory Bowel Diseases, we discovered loss-of-function variants in CARD9 and RNF186 that protect against Crohn&#8217;s disease [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-135","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/posts\/135","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/comments?post=135"}],"version-history":[{"count":3,"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/posts\/135\/revisions"}],"predecessor-version":[{"id":217,"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/posts\/135\/revisions\/217"}],"wp:attachment":[{"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/media?parent=135"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/categories?post=135"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/mrivas.su.domains\/gbe\/wp-json\/wp\/v2\/tags?post=135"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}