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10.1038/s41591-021-01310-z http://scihub22266oqcxt.onion/10.1038/s41591-021-01310-z 33837377!7612986!33837377     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Med 2021 ; 27 (4): 668-676 Nephropedia Template TP {{tp|p=33837377|t=2021. Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19 |pdf=|usr=}}{{33837377}} gab.com Text Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19 JO: Nat Med http://www.kidney.de/pget.php?&tw=1&pmid=33837377 #FOAvip Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19. Twit Text FOAVip Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19 ????Nat Med http://www.kidney.de/pget.php?&tw=1&pmid=33837377 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33837377 #FOAvip English Wikipedia <ref>{{Cite pmid|33837377}}</ref> Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19 #MMPMID33837377 Gaziano L; Giambartolomei C; Pereira AC; Gaulton A; Posner DC; Swanson SA; Ho YL; Iyengar SK; Kosik NM; Vujkovic M; Gagnon DR; Bento AP; Barrio-Hernandez I; Ronnblom L; Hagberg N; Lundtoft C; Langenberg C; Pietzner M; Valentine D; Gustincich S; Tartaglia GG; Allara E; Surendran P; Burgess S; Zhao JH; Peters JE; Prins BP; Angelantonio ED; Devineni P; Shi Y; Lynch KE; DuVall SL; Garcon H; Thomann LO; Zhou JJ; Gorman BR; Huffman JE; O'Donnell CJ; Tsao PS; Beckham JC; Pyarajan S; Muralidhar S; Huang GD; Ramoni R; Beltrao P; Danesh J; Hung AM; Chang KM; Sun YV; Joseph J; Leach AR; Edwards TL; Cho K; Gaziano JM; Butterworth AS; Casas JP Nat Med 2021[Apr]; 27 (4): 668-676 PMID33837377show ga Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19. |*Drug Repositioning[MESH] |*SARS-CoV-2[MESH] |Angiotensin-Converting Enzyme 2/genetics/physiology[MESH] |COVID-19 Drug Treatment[MESH] |COVID-19/*genetics[MESH] |Genome-Wide Association Study[MESH] |Humans[MESH] |Interleukin-10 Receptor beta Subunit/genetics/physiology[MESH] |Mendelian Randomization Analysis/*methods[MESH] |Quantitative Trait Loci[MESH]Actionable druggable genome-wide Mendelian randomization identifies re(epmc).pdf DeepDyve Pubget Overpricing