{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T08:27:19Z","timestamp":1772267239805,"version":"3.50.1"},"reference-count":43,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["VR-2018-02247"],"award-info":[{"award-number":["VR-2018-02247"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006636","name":"Swedish Research Council for Health, Working Life and Welfare","doi-asserted-by":"publisher","award":["FORTE-2020-00884"],"award-info":[{"award-number":["FORTE-2020-00884"]}],"id":[{"id":"10.13039\/501100006636","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>To understand a causal role of modifiable lifestyle factors in angiotensin-converting enzyme 2 (ACE2) expression (a putative severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] receptor) across 44 human tissues\/organs, and in coronavirus disease 2019 (COVID-19) susceptibility and severity, we conducted a phenome-wide two-sample Mendelian randomization (MR) study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>More than 500 genetic variants were used as instrumental variables to predict smoking and alcohol consumption. Inverse-variance weighted approach was adopted as the primary method to estimate a causal association, while MR-Egger regression, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to identify potential horizontal pleiotropy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We found that genetically predicted smoking intensity significantly increased ACE2 expression in thyroid (\u03b2=1.468, p=1.8\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ), and increased ACE2 expression in adipose, brain, colon, and liver with nominal significance. Additionally, genetically predicted smoking initiation significantly increased the risk of COVID-19 onset (odds ratio=1.14, p=8.7\u00d710\n                      <jats:sup>\u22125<\/jats:sup>\n                      ). No statistically significant result was observed for alcohol consumption.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our work demonstrates an important role of smoking, measured by both status and intensity, in the susceptibility to COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>XJ is supported by research grants from the Swedish Research Council (VR-2018\u201302247) and Swedish Research Council for Health, Working Life and Welfare (FORTE-2020\u201300884).<\/jats:p>\n                  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