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

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=5.93x10-7) and very severe hospitalized COVID-19 (OR=3.091, 95% CI, 1.883-5.092, P-value=8.40x10-6). Genetically predicted lifetime smoking was also associated with increased risk pneumoniae (OR=1.589, 95% CI, 1.214-2.078, P-value=7.33x10-4), lower respiratory infections (OR=2.303, 95% CI, 1.713-3.097, P-value=3.40x10-8), 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.

SUBMITTER: Rosoff DB

PROVIDER: S-EPMC7885939 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Rosoff Daniel B DB Yoo Joyce J Lohoff Falk W FW

medRxiv : the preprint server for health sciences 20210212

<h4>Background</h4>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.<h4>Methods</h4>Using genome-wide association study data of European ancestry (data from >1.7 million individuals), we performed single-variable and multivariable Mende ...[more]

PMID: 33594380

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Project description:Background and aimsWhile epidemiological studies support a role for heavy, high-potency cannabis use on first-episode psychosis, genetic models of causation suggest reverse causal effects of schizophrenia on cannabis use liability. We estimated the genetic relationship between cannabis use disorder (CUD) and schizophrenia (SCZ) and tested whether liability for CUD is causally associated with increased liability to SCZ while adjusting for tobacco smoking.DesignThis study used summary statistics from published genome-wide association studies (GWAS). We used genomic structural equation modeling, latent causal variable analysis, and multivariable Mendelian randomization to examine genetic relationships between CUD, cannabis ever-use, ever-smoked tobacco regularly, nicotine dependence and SCZ, and to test for a causal relationship between liability to CUD and liability to SCZ.SettingGenome-wide association studies were published previously as part of international consortia.ParticipantsSample sizes of the GWAS summary statistics used in this study ranged from 161 405 to 357 806 individuals of European ancestry.MeasurementsGenome-wide summary statistics for CUD and SCZ were the primary measurements, while summary statistics for cannabis ever-use, ever-smoked tobacco regularly and nicotine dependence were included as additional variables in the genomic structural equation models and the multivariable Mendelian randomization analyses.FindingsGenetic liability to CUD was significantly associated with SCZ [β = 0.29, 95% confidence interval (CI) = 0.11, 0.46, P = 0.001], even when accounting for cannabis ever-use, ever-smoked tobacco regularly and nicotine dependence as simultaneous predictors. We found mixed evidence of a causal relationship, with the latent causal variable analysis finding no evidence of causality (genetic causality proportion = -0.08, 95% CI = -0.40, 0.23, P = 0.87) but the multivariable Mendelian randomization analyses suggesting a significant, risk-increasing effect of CUD on liability to SCZ (β = 0.10, 95% CI = 0.02, 0.18, P = 0.02), accounting for the additional risk factors (cannabis ever-use, ever-smoked tobacco regularly and nicotine dependence).ConclusionsGenetic liability for cannabis use disorder appears to be robustly associated with schizophrenia, above and beyond tobacco smoking and cannabis ever-use, with mixed evidence to support a causal relationship between cannabis use disorder and schizophrenia.

Project description:As in many other countries worldwide, the coronavirus pandemic prompted the implementation of an "intelligent lockdown" in the spring of 2020 in the Netherlands, including the closure of nightlife venues and cancellation of festivals. Such restrictions and social distancing could particularly affect people who use alcohol or other drugs in recreational settings and give rise to new challenges and additional needs in the field of addiction prevention and care. To monitor changes in substance use and provide services with practical directions for tailored prevention, an anonymous web survey was set up, targeting a convenience sample aged 16 years or older through various social media and other online channels. Between May and October 2020, a total of 6,070 participants completed the survey, mainly adolescents and young adults (16-24 years old). These data were used to explore and describe changing patterns in substance use. Overall results showed declined current use compared to "pre-corona," but mask underlying variation in changing patterns, including discontinued (tobacco 10.4%, alcohol 11.3%, cannabis 16.3%, other drugs 30.4%), decreased (tobacco 23.0%, alcohol 29.1%, cannabis 17.4%, other drugs 20.7%), unchanged (tobacco 30.3%, alcohol 21.2%, cannabis 22.3%, other drugs 17.3%), increased (tobacco 29.6%, alcohol 32.1%, cannabis 32.9%, other drugs 25.3%), and (re)commenced use (tobacco 6.7%, alcohol 6.3%, cannabis 11.1%, other drugs 6.2%). Especially the use of drugs like ecstasy and nitrous oxide was discontinued or decreased due to the lack of social occasions for use. Increased use was associated with coping motives for all substance types. As measures combatting the coronavirus may need to be practiced for some time to come, possibly leading to prolonged changes in substance use with lingering "post-corona" consequences, timely and ongoing monitoring of changing patterns of substance use is vital for informing prevention services within this field.

Dataset Information

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

Publications

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

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