Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19.
PLoS Genet
; 18(3): e1010042, 2022 03.
Article
in English
| MEDLINE | ID: covidwho-1793655
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Blood Proteins
/
COVID-19
Type of study:
Diagnostic study
/
Experimental Studies
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
PLoS Genet
Journal subject:
Genetics
Year:
2022
Document Type:
Article
Affiliation country:
Journal.pgen.1010042
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