Does ACE2 mediate the detrimental effect of exposures related to COVID-19 risk: A Mendelian randomization investigation.
J Med Virol
; 2022 Oct 10.
Article
in English
| MEDLINE | ID: covidwho-2227734
ABSTRACT
OBJECTIVES:
Adiposity, smoking, and lower socioeconomic position (SEP) increase COVID-19 risk while the association of vitamin D, blood pressure, and glycemic traits in COVID-19 risk were less clear. Whether angiotensin-converting enzyme 2 (ACE2), the key receptor for SARS-CoV-2, mediates these associations has not been investigated. We conducted a Mendelian randomization study to assess the role of these exposures in COVID-19 and mediation by ACE2.METHODS:
We extracted genetic variants strongly related to various exposures (vitamin D, blood pressure, glycemic traits, smoking, adiposity, and educational attainment [SEP proxy]), and ACE2 cis-variants from genome-wide association studies (GWAS, n ranged from 28 204 to 3 037 499) and applied them to GWAS summary statistics of ACE2 (n = 28 204) and COVID-19 (severe, hospitalized, and susceptibility, n ≤ 2 942 817). We used inverse variance weighted as the main analyses, with MR-Egger and weighted median as sensitivity analyses. Mediation analyses were performed based on product of coefficient method.RESULTS:
Higher adiposity, lifetime smoking index, and lower educational attainment were consistently associated with higher risk of COVID-19 phenotypes while there was no strong evidence for an association of other exposures in COVID-19 risk. ACE2 partially mediates the detrimental effects of body mass index (ranged from 4.3% to 8.2%), waist-to-hip ratio (ranged from 11.2% to 16.8%), and lower educational attainment (ranged from 4.0% to 7.5%) in COVID-19 phenotypes while ACE2 did not mediate the detrimental effect of smoking.CONCLUSIONS:
We provided genetic evidence that reducing ACE2 could partly lower COVID-19 risk amongst people who were overweight/obese or of lower SEP.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Variants
Language:
English
Year:
2022
Document Type:
Article
Affiliation country:
Jmv.28205
Similar
MEDLINE
...
LILACS
LIS