A genetically-informed study disentangling the relationships between tobacco smoking, cannabis use, alcohol consumption, substance use disorders and respiratory infections, including COVID-19

  1. Daniel B. Rosoff
  2. Joyce Yoo
  3. Falk W. Lohoff

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Abstract

Background

Observational studies suggest smoking, cannabis use, alcohol consumption, cannabis use, and substance use disorders (SUDs) may play a role in the susceptibility for respiratory infections and disease, including coronavirus 2019 (COVID-2019). However, causal inference is challenging due to comorbid substance use.

Methods

Using genome-wide association study data of European ancestry (data from >1.7 million individuals), we performed single-variable and multivariable Mendelian randomization to evaluate relationships between smoking, cannabis use, alcohol consumption, SUDs, and respiratory infections.

Results

Genetically predicted lifetime smoking was found to be associated with increased risk for hospitalized COVID-19 (odds ratio (OR)=4.039, 95% CI 2.335-6.985, P -value=5.93×10 −7 ) and very severe hospitalized COVID-19 (OR=3.091, 95% CI, 1.883-5.092, P -value=8.40×10 −6 ). Genetically predicted lifetime smoking was also associated with increased risk pneumoniae (OR=1.589, 95% CI, 1.214-2.078, P -value=7.33×10 −4 ), lower respiratory infections (OR=2.303, 95% CI, 1.713-3.097, P -value=3.40×10 −8 ), and several others. Genetically predicted cannabis use disorder (CUD) was associated with increased bronchitis risk (OR=1.078, 95% CI, 1.020-1.128, P -value=0.007).

Conclusions

We provide strong genetic evidence showing smoking increases the risk for respiratory infections and diseases even after accounting for other substance use and abuse. Additionally, we provide find CUD may increase the risk for bronchitis, which taken together, may guide future research SUDs and respiratory outcomes.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.11.21251581: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Detailed documentation is provided on the FinnGen study website (https://finngen.gitbook.io/documentation/).
    FinnGen
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study also has limitations: For example, like existing self-reported substance use literature, these exposures may be either under- or over-reported.70 Because many of the datasets included UK Biobank participants, who are more educated, with healthier lifestyles, and fewer health problems than the UK population,71 which may limit the applicability of our findings to other populations. Regarding our mainly null alcohol-respiratory infection results, it is possible that alcohol may have indirect impact on infection risk through a modified immune response,72 or other system dysregulation, that may modulate infection risk that we were not able to directly assess. Further, while we found some evidence that AUD may increase the risk for COVID-19; the largely null other current AUD findings does not support a broader AUD-respiratory disease relationship. However, like other recent psychiatric MR studies where the exposure instruments included a relaxed statistical threshold, our binge drinking and AUD instruments were comprised of independent SNPs associated with the respective drinking behavior (i.e., P-value < 5×10−6) for SNP inclusion due to the lack of conventionally GWS SNPs (P-value < 5×10−8),29,30 which may impact the results. Because heavy alcohol consumption and AUD have been previously linked with acute respiratory distress syndrome10 – one of the most severe complications of COVID-19,73 future studies re-evaluating the links between heavy alcohol consumption and AUD...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2021.02.11.21251581v1 on medRxiv