Dataset Information

Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization.

ABSTRACT:

Rationale & objective

The association between cannabis use and chronic kidney disease (CKD) is controversial. We aimed to assess association of CKD with cannabis use in a large cohort study and then assess causality using Mendelian randomization with a genome-wide association study (GWAS).

Study design

Retrospective cohort study and genome-wide association study.

Setting & participants

The retrospective study was conducted on the All of Us cohort (N=223,354). Genetic instruments for cannabis use disorder were identified from 3 GWAS: the Psychiatric Genomics Consortium Substance Use Disorders, iPSYCH, and deCODE (N=384,032). Association between genetic instruments and CKD was investigated in the CKDGen GWAS (N > 1.2 million).

Exposure

Cannabis consumption.

Outcomes

CKD outcomes included: cystatin-C and creatinine-based kidney function, proteinuria, and blood urea nitrogen.

Analytical approach

We conducted association analyses to test for frequency of cannabis use and CKD. To evaluate causality, we performed a 2-sample Mendelian randomization.

Results

In the retrospective study, compared to former users, less than monthly (OR, 1.01; 95% CI, 0.87-1.18; P = 0.87) and monthly cannabis users (OR, 1.15; 95% CI, 0.86-1.52; P = 0.33) did not have higher CKD odds. Conversely, weekly (OR, 1.28; 95% CI, 1.01-1.60; P = 0.04) and daily use (OR, 1.25; 95% CI, 1.04-1.50; P = 0.02) was significantly associated with CKD, adjusted for multiple confounders. In Mendelian randomization, genetic liability to cannabis use disorder was not associated with increased odds for CKD (OR, 1.00; 95% CI, 0.99-1.01; P = 0.96). These results were robust across different Mendelian randomization techniques and multiple kidney traits.

Limitations

Likely underreporting of cannabis use. In Mendelian randomization, genetic instruments were identified in the GWAS that included individuals primarily of European ancestry.

Conclusions

Despite the epidemiological association between cannabis use and CKD, there was no evidence of a causal effect, indicating confounding in observational studies.

SUBMITTER: Dellepiane S

PROVIDER: S-EPMC9879977 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization.

Dellepiane Sergio S Paranjpe Ishan I Rajagopal Madhumitha M Kamat Samir S O'Hagan Ross R Gulamali Faris F Rein Joshua L JL Charney Alexander W AW Do Ron R Coca Steven S Glicksberg Benjamin S BS Nadkarni Girish N GN

Kidney medicine 20221211 2

<h4>Rationale & objective</h4>The association between cannabis use and chronic kidney disease (CKD) is controversial. We aimed to assess association of CKD with cannabis use in a large cohort study and then assess causality using Mendelian randomization with a genome-wide association study (GWAS).<h4>Study design</h4>Retrospective cohort study and genome-wide association study.<h4>Setting & participants</h4>The retrospective study was conducted on the All of Us cohort (N=223,354). Genetic instru ...[more]

PMID: 36712313

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Project description:BackgroundThe use of cannabis has increased globally due to more regions decriminalizing marijuana use for therapeutic and recreational aims. Several observational studies have revealed that cannabis use is associated with an increased risk of adverse cardiovascular pathologies and diseases. Nevertheless, the causal associations between cannabis use and cardiovascular diseases remain unclear. Hence, we performed single-variable and multivariable Mendelian randomization (MR) to evaluate the association between cannabis use disorder and various cardiovascular diseases.Materials and methodsSummary statistics were collected from the largest-to-date genome-wide association studies (GWAS) of cannabis use disorder. The 12 SNPs for cannabis use disorder were used as instrumental variables in this study. MR estimates were pooled using a random-effects inverse-variance weighted (IVW) method. Simple median and weighted median methods were conducted as sensitivity analyses.ResultsThe genetic liability to cannabis use disorder was associated with an augmented risk of coronary artery disease, myocardial infarction, atrial fibrillation, heart failure, deep venous thrombosis, pulmonary embolism, and stroke. Except for stroke, the results were inconsistent in the sensitivity analyses. The overall patterns for the associations of cannabis use disorder with atrial fibrillation, heart failure, pulmonary embolism and stroke remained in multivariable MR analyses adjusting for potential mediators, including smoking, alcohol, body mass index, blood lipid, type 2 diabetes, hypertension, and depression. However, the association with coronary artery disease, myocardial infarction, and deep venous thrombosis did not persist in multivariable MR analyses. Mediation analysis demonstrated that smoking, body mass index, low-density lipoprotein, hypertension, and depression have more significant mediation effects, which suggests that these factors partly mediate the link from cannabis use disorder to coronary artery disease, myocardial infarction, and deep venous thrombosis.ConclusionThe genetic liability to cannabis use disorder was associated with a higher risk of atrial fibrillation, heart failure, pulmonary embolism, and stroke. The evidence for the association between cannabis use disorder, coronary artery disease, myocardial infarction, and deep venous thrombosis was weak. Hence, future use of cannabis for therapeutic and recreational aims should consider its potential impact on cardiovascular diseases.

Dataset Information

Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization.

Rationale & objective

Study design

Setting & participants

Exposure

Outcomes

Analytical approach

Results

Limitations

Conclusions

Publications

Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization.

Similar Datasets

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