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@article{Gaziano:2021:10.1038/s41591-021-01310-z,
author = {Gaziano, L and Giambartolomei, C and Pereira, AC and Gaulton, A and Posner, DC and Swanson, SA and Ho, Y-L and Iyengar, SK and Kosik, NM and Vujkovic, M and Gagnon, DR and Bento, AP and Barrio-Hernandez, I and Rönnblom, L and Hagberg, N and Lundtoft, C and Langenberg, C and Pietzner, M and Valentine, D and Gustincich, S and Tartaglia, GG and Allara, E and Surendran, P and Burgess, S and Zhao, JH and Peters, JE and Prins, BP and Angelantonio, ED and Devineni, P and Shi, Y and Lynch, KE and DuVall, SL and Garcon, H and Thomann, LO and Zhou, JJ and Gorman, BR and Huffman, JE and O'Donnell, CJ and Tsao, PS and Beckham, JC and Pyarajan, S and Muralidhar, S and Huang, GD and Ramoni, R and Beltrao, P and Danesh, J and Hung, AM and Chang, K-M and Sun, YV and Joseph, J and Leach, AR and Edwards, TL and Cho, K and Gaziano, JM and Butterworth, AS and Casas, JP and VA, Million Veteran Program COVID-19 Science Initiative},
doi = {10.1038/s41591-021-01310-z},
journal = {Nat Med},
pages = {668--676},
title = {Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19.},
url = {http://dx.doi.org/10.1038/s41591-021-01310-z},
volume = {27},
year = {2021}
}

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TY  - JOUR
AB  - 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 × 10-6; IFNAR2, P = 9.8 × 10-11 and IL-10RB, P = 2.3 × 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.
AU  - Gaziano,L
AU  - Giambartolomei,C
AU  - Pereira,AC
AU  - Gaulton,A
AU  - Posner,DC
AU  - Swanson,SA
AU  - Ho,Y-L
AU  - Iyengar,SK
AU  - Kosik,NM
AU  - Vujkovic,M
AU  - Gagnon,DR
AU  - Bento,AP
AU  - Barrio-Hernandez,I
AU  - Rönnblom,L
AU  - Hagberg,N
AU  - Lundtoft,C
AU  - Langenberg,C
AU  - Pietzner,M
AU  - Valentine,D
AU  - Gustincich,S
AU  - Tartaglia,GG
AU  - Allara,E
AU  - Surendran,P
AU  - Burgess,S
AU  - Zhao,JH
AU  - Peters,JE
AU  - Prins,BP
AU  - Angelantonio,ED
AU  - Devineni,P
AU  - Shi,Y
AU  - Lynch,KE
AU  - DuVall,SL
AU  - Garcon,H
AU  - Thomann,LO
AU  - Zhou,JJ
AU  - Gorman,BR
AU  - Huffman,JE
AU  - O'Donnell,CJ
AU  - Tsao,PS
AU  - Beckham,JC
AU  - Pyarajan,S
AU  - Muralidhar,S
AU  - Huang,GD
AU  - Ramoni,R
AU  - Beltrao,P
AU  - Danesh,J
AU  - Hung,AM
AU  - Chang,K-M
AU  - Sun,YV
AU  - Joseph,J
AU  - Leach,AR
AU  - Edwards,TL
AU  - Cho,K
AU  - Gaziano,JM
AU  - Butterworth,AS
AU  - Casas,JP
AU  - VA,Million Veteran Program COVID-19 Science Initiative
DO  - 10.1038/s41591-021-01310-z
EP  - 676
PY  - 2021///
SP  - 668
TI  - Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19.
T2  - Nat Med
UR  - http://dx.doi.org/10.1038/s41591-021-01310-z
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33837377
UR  - http://hdl.handle.net/10044/1/87573
VL  - 27
ER  -

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