Genetic analysis links cannabis use disorder to higher risk of atrial fibrillation, heart failure, and stroke

Genetic liability to cannabis use disorder was associated with higher risk of atrial fibrillation, heart failure, pulmonary embolism, and stroke in both univariable and multivariable MR analyses adjusting for smoking, alcohol, BMI, lipids, diabetes, hypertension, and depression. Initial associations with coronary artery disease, myocardial infarction, and deep venous thrombosis did not persist after adjustment, suggesting mediation by traditional cardiovascular risk factors.

Two-sample Mendelian randomization using 12 SNPs from the largest GWAS of cannabis use disorder as instrumental variables. Cardiovascular outcomes from published GWAS. Inverse-variance weighted method with sensitivity analyses. Multivariable MR adjusted for potential mediators.

Mendelian randomization reduces confounding compared to observational studies. Finding that cannabis use disorder has cardiovascular risks independent of traditional risk factors strengthens the case for a causal relationship.

While many cardiovascular risks of cannabis may be driven by co-occurring factors like smoking and obesity, the independent associations with atrial fibrillation and stroke suggest direct cardiovascular effects that warrant further investigation.

MR instruments for cannabis use disorder may capture pleiotropic effects. Cannot distinguish cannabis use disorder from occasional use. European ancestry samples limit generalizability. Some sensitivity analyses were inconsistent.