A Mendelian randomization study found that genetic predisposition to bipolar disorder increased the likelihood of trying cannabis, but genetic predisposition to cannabis use did not increase bipolar risk.
Psychiatric genetics researchers and clinicians treating bipolar disorder with comorbid cannabis use.
Bipolar genetics predicted cannabis use, but not the reverse
What the researchers found
Genetic liability to bipolar disorder was significantly associated with increased risk of lifetime cannabis use across all three MR methods (inverse variance weighted, weighted median, and Egger regression). In contrast, genetic liability to lifetime cannabis use showed no association with bipolar disorder risk. Sensitivity analyses found no evidence of confounding through pleiotropic effects.
Why it matters
Previous MR studies examined cannabis and schizophrenia, depression, and ADHD, but not bipolar disorder. This study fills that gap and finds a unidirectional relationship: bipolar vulnerability drives cannabis use, not the other way around. This has implications for understanding self-medication in bipolar disorder.
The numbers in context
Genetic instruments from large GWAS studies. Bipolar disorder genetic liability significantly predicted lifetime cannabis use across all three MR methods. Cannabis use genetic liability showed no significant effect on bipolar disorder risk. No evidence of pleiotropy in sensitivity analyses.
How the study worked
Two-sample bidirectional Mendelian randomization using genome-wide significant SNPs from large GWAS of bipolar disorder and lifetime cannabis use. Three complementary MR methods applied with sensitivity analyses for pleiotropy.
What this study cannot tell us
Mendelian randomization assumes genetic instruments only affect the outcome through the exposure (exclusion restriction). Lifetime cannabis use (ever vs. never) is a crude measure. Cannot examine heavy use or CUD specifically. Population-level finding may not apply to individuals.
How to read the evidence
Well-executed bidirectional MR with appropriate sensitivity analyses. Moderate because MR has inherent assumptions and uses crude lifetime use measure.
When this study was published
2021 Mendelian randomization study using large GWAS data.
The bigger picture
The finding that bipolar genetics drives cannabis use (but not vice versa) contrasts with the cannabis-schizophrenia relationship, where evidence suggests bidirectional effects. This means the cannabis-bipolar association may primarily reflect self-medication rather than cannabis causing bipolar disorder.
Questions still open
- Would MR with cannabis use disorder (rather than any use) show different results? What aspects of bipolar vulnerability drive cannabis use? Does cannabis worsen bipolar course even if it does not cause onset?
Common questions
Does cannabis cause bipolar disorder?
How is this different from the cannabis-schizophrenia relationship?
Read the original research
Bipolar disorder and cannabis use: A bidirectional two-sample Mendelian randomization study.
Addiction biology, 26(6), e13030
Citation
Jefsen, Oskar Hougaard; Speed, Maria; Speed, Doug; Østergaard, Søren Dinesen. (2021). Bipolar disorder and cannabis use: A bidirectional two-sample Mendelian randomization study.. Addiction biology, 26(6), e13030. https://doi.org/10.1111/adb.13030
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