key: cord-0840781-6w6btora authors: Zheng, B.-K.; Li, N. title: Smoking and COVID-19: A two-sample Mendelian randomization study date: 2021-04-06 journal: nan DOI: 10.1101/2021.03.31.21254730 sha: c2cca2b22d8a9f76bd99917a683928599e5b981c doc_id: 840781 cord_uid: 6w6btora Evidence from observational studies suggested that smokers are at increased risk of coronavirus disease 2019 (COVID-19). We aimed to assess the causal effect of smoking on risk for COVID-19 susceptibility and severity using two-sample Mendelian randomization method. Smoking-associated variants were selected as instrument variables from two largest genetic studies. The latest summary data of COVID-19 that shared on Jan 18, 2021 by the COVID-19 Host Genetics Initiative was used. The present Mendelian randomization study provided genetic evidence that smoking was a causal risk factor for COVID-19 susceptibility and severity. In addition, there may be a dose-effect relationship between smoking and COVID-19 severity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.03.31.21254730 doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. Evidence from observational studies suggested that smokers are at increased risk of coronavirus disease 2019 . We aimed to assess the causal effect of smoking on risk for COVID-19 susceptibility and severity using two-sample Mendelian randomization method. Smoking-associated variants were selected as instrument variables from two largest genetic studies. The latest summary data of COVID-19 that shared on Jan 18, 2021 by the COVID-19 Host Genetics Initiative was used. The present Mendelian randomization study provided genetic evidence that smoking was a causal risk factor for COVID-19 susceptibility and severity. In addition, there may be a dose-effect relationship between smoking and COVID-19 severity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 6, 2021. Evidence from observational studies suggested that smokers are at increased risk of coronavirus disease 2019 (COVID-19) (1, 2) . Two-sample Mendelian randomization (MR) study could be used to assess the effect of smoking on risk of COVID-19 because it could assess causality and could limit the bias caused by confounders (3). We aimed to assess the causal effect of smoking on risk for COVID-19 susceptibility and severity using two-sample MR method. Four following measures of smoking were chosen as exposures: smoking initiation: defined as ever being a regular smoker; lifetime smoking: a continuous variable that accounting for smoking status, age at smoking initiation and cessation, cigarettes per day, and a simulated half-life constant effected on health outcomes; cigarettes per day: Additional sensitivity analysis was performed by excluding SNPs associated (p < 5×10 -8 ) with body mass index (BMI) because previous MR study showed BMI was the only one cardiometabolic factor that associated with COVID-19 (7). P value of MR analysis small than 0.003 (0.05/16) was considered as statistically significant. P value of MR analysis small than 0.05 was considered as nominally significant. Main MR analyses showed smoking initiation was significantly or nominally associated with outcomes of COVID-19 cases vs. population controls, hospitalized COVID-19 cases vs. population controls, and very severe respiratory confirmed . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. We could not assess the effect of current smoking and former smoking separately because the data was not available. Meta-analyses suggested that current smokers had higher odds compared with non-current smokers but lower odds compared with former smokers for COVID-19 susceptibility and adverse outcome (1, 2) . This finding was not supported by the present study because the present study showed current smoking was not associated with decreased risk of COVID-19 susceptibility and . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.03.31.21254730 doi: medRxiv preprint severity compared with former smoking. However, the statistical power is relatively small for exposure of smoking cessation in the present study. In addition, time since cessation may also associated with COVID-19 risk (1) . The present MR study provided genetic evidence that smoking was a causal risk factor for COVID-19 susceptibility and severity. In addition, there may be a dose-effect relationship between smoking and COVID-19 severity. Financial support information: None. We thank the COVID-19 Host Genetics Initiative and all other contributors for making summary statistics publicly accessible. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.03.31.21254730 doi: medRxiv preprint The association of smoking status with sars-cov-2 infection, hospitalization and mortality from covid-19: A living rapid evidence review with bayesian meta-analyses Current smoking, former smoking, and adverse outcome among hospitalized covid-19 patients: A systematic review and meta-analysis The mr-base platform supports systematic causal inference across the human phenome Evidence for causal effects . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. For exposure of lifetime smoking, we used summary data of COVID-19 that excluding UK biobank data.. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 6, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted April 6, 2021. ; https://doi.org/10.1101/2021.03.31.21254730 doi: medRxiv preprint