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Article: Does ACE2 mediate the detrimental effect of exposures related to COVID‐19 risk: A Mendelian randomization investigation

TitleDoes ACE2 mediate the detrimental effect of exposures related to COVID‐19 risk: A Mendelian randomization investigation
Authors
KeywordsACE2
COVID-19
genetics
mediation
Mendelian randomization
Issue Date2022
Citation
Journal of Medical Virology, 2022 How to Cite?
AbstractObjectives: 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.
Persistent Identifierhttp://hdl.handle.net/10722/319109
ISSN
2023 Impact Factor: 6.8
2023 SCImago Journal Rankings: 1.560
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorAu Yeung, SLR-
dc.contributor.authorWong, HT-
dc.contributor.authorHe, B-
dc.contributor.authorLuo, S-
dc.contributor.authorKwok, KO-
dc.date.accessioned2022-10-14T05:07:17Z-
dc.date.available2022-10-14T05:07:17Z-
dc.date.issued2022-
dc.identifier.citationJournal of Medical Virology, 2022-
dc.identifier.issn0146-6615-
dc.identifier.urihttp://hdl.handle.net/10722/319109-
dc.description.abstractObjectives: 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.-
dc.languageeng-
dc.relation.ispartofJournal of Medical Virology-
dc.subjectACE2-
dc.subjectCOVID-19-
dc.subjectgenetics-
dc.subjectmediation-
dc.subjectMendelian randomization-
dc.titleDoes ACE2 mediate the detrimental effect of exposures related to COVID‐19 risk: A Mendelian randomization investigation-
dc.typeArticle-
dc.identifier.emailAu Yeung, SLR: ayslryan@hku.hk-
dc.identifier.emailWong, HT: thtwong@hku.hk-
dc.identifier.emailHe, B: hbaoting@hku.hk-
dc.identifier.emailLuo, S: aprilluo@hku.hk-
dc.identifier.authorityAu Yeung, SLR=rp02224-
dc.identifier.doi10.1002/jmv.28205-
dc.identifier.pmid36217700-
dc.identifier.scopuseid_2-s2.0-85140226982-
dc.identifier.hkuros339138-
dc.identifier.isiWOS:000870351700001-

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