{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T15:37:33Z","timestamp":1780673853128,"version":"3.54.1"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471364"],"award-info":[{"award-number":["81471364"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We aimed to investigate the genetic mechanisms associated with coronavirus disease of 2019 (COVID-19) outcomes in the host and to evaluate the possible associations between smoking and drinking behavior and three COVID-19 outcomes: severe COVID-19, hospitalized COVID-19 and COVID-19 infection. We described the genomic loci and risk genes associated with the COVID-19 outcomes, followed by functional analyses of the risk genes. Then, a summary data-based Mendelian randomization (SMR) analysis, and a transcriptome-wide association study (TWAS) were performed for the severe COVID-19 dataset. A two-sample Mendelian randomization (MR) analysis was used to evaluate the causal associations between various measures of smoking and alcohol consumption and the COVID-19 outcomes. A total of 26 protein-coding genes, enriched in chemokine binding, cytokine binding and senescence-related functions, were associated with either severe COVID-19 or hospitalized COVID-19. The SMR and the TWAS analyses highlighted functional implications of some GWAS hits and identified seven novel genes for severe COVID-19, including CCR5, CCR5AS, IL10RB, TAC4, RMI1 and TNFSF15, some of which are targets of approved or experimental drugs. According to our studies, increasing consumption of cigarettes per day by 1 standard deviation is related to a 2.3-fold increase in susceptibility to severe COVID-19 and a 1.6-fold increase in COVID-19-induced hospitalization. Contrarily, no significant links were found between alcohol consumption or binary smoking status and COVID-19 outcomes. Our study revealed some novel COVID-19 related genes and suggested that genetic liability to smoking may quantitatively contribute to an increased risk for a severe course of COVID-19.<\/jats:p>","DOI":"10.1093\/bib\/bbab284","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T11:12:43Z","timestamp":1625483563000},"source":"Crossref","is-referenced-by-count":36,"title":["Genetic mechanisms of COVID-19 and its association with smoking and alcohol consumption"],"prefix":"10.1093","volume":"22","author":[{"given":"Shuquan","family":"Rao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ancha","family":"Baranova","sequence":"additional","affiliation":[{"name":"School of Systems Biology, George Mason University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbao","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Systems Biology, George Mason University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiu","family":"Chen","sequence":"additional","affiliation":[{"name":"Affiliated Brain Hospital of Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangrong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Brain Hospital of Nanjing Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Brain Hospital of Nanjing Medical University, 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