Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19.



Palmos, Alish B, Millischer, Vincent, Menon, David K, Nicholson, Timothy R, Taams, Leonie S, Michael, Benedict ORCID: 0000-0002-8693-8926, Sunderland, Geraint ORCID: 0000-0001-9040-5949, Griffiths, Michael J, COVID Clinical Neuroscience Study Consortium, , Hübel, Christopher
et al (show 1 more authors) (2022) Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19. PLoS genetics, 18 (3). e1010042-e1010042.

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Abstract

In November 2021, the COVID-19 pandemic death toll surpassed five million individuals. We applied Mendelian randomization including >3,000 blood proteins as exposures to identify potential biomarkers that may indicate risk for hospitalization or need for respiratory support or death due to COVID-19, respectively. After multiple testing correction, using genetic instruments and under the assumptions of Mendelian Randomization, our results were consistent with higher blood levels of five proteins GCNT4, CD207, RAB14, C1GALT1C1, and ABO being causally associated with an increased risk of hospitalization or respiratory support/death due to COVID-19 (ORs = 1.12-1.35). Higher levels of FAAH2 were solely associated with an increased risk of hospitalization (OR = 1.19). On the contrary, higher levels of SELL, SELE, and PECAM-1 decrease risk of hospitalization or need for respiratory support/death (ORs = 0.80-0.91). Higher levels of LCTL, SFTPD, KEL, and ATP2A3 were solely associated with a decreased risk of hospitalization (ORs = 0.86-0.93), whilst higher levels of ICAM-1 were solely associated with a decreased risk of respiratory support/death of COVID-19 (OR = 0.84). Our findings implicate blood group markers and binding proteins in both hospitalization and need for respiratory support/death. They, additionally, suggest that higher levels of endocannabinoid enzymes may increase the risk of hospitalization. Our research replicates findings of blood markers previously associated with COVID-19 and prioritises additional blood markers for risk prediction of severe forms of COVID-19. Furthermore, we pinpoint druggable targets potentially implicated in disease pathology.

Item Type: Article
Uncontrolled Keywords: COVID Clinical Neuroscience Study Consortium
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 06 Apr 2022 10:39
Last Modified: 31 May 2023 15:11
DOI: 10.1371/journal.pgen.1010042
Open Access URL: https://doi.org/10.1371/journal.pgen.1010042
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3152253