Genetic support of a causal relationship between cannabis use and educational attainment: a two-sample Mendelian randomization study of European ancestry.

BACKGROUND AND AIMS
Excessive cannabis use may lead to lower educational attainment. However, this association may be due to confounders and reverse causality. We tested the potential causal relationship between cannabis use disorder (CUD) or lifetime cannabis use (LCU) and educational attainment.


DESIGN
Bidirectional two-sample Mendelian randomization (MR) study. Our primary method was inverse-variance weighted (IVW) MR, with a series of sensitivity analyses. Multivariable MR (MVMR) was performed to estimate any direct effect independent of intelligence, smoking initiation or attention deficit hyperactivity disorder (ADHD).


SETTING AND PARTICIPANTS
European ancestry individuals. The sample sizes of the genome-wide association study ranged from 55374 to 632802 participants.


MEASUREMENTS
Genetic variants of CUD, LCU or educational attainment.


FINDINGS
Using univariable MR, we found evidence of a potential causal effect of genetic liability to CUD on a lower educational attainment (MR [95% confidence interval (CI)]inverse variance weighted (IVW) = -1.2 month [-1.9 month, -0.5 month]; P = 0.0008). However, we found no evidence of an effect of genetic liability to LCU on educational attainment (MR [95% CI]IVW = 0.5 month [-1.5 month, 2.6 month], P = 0.6032). Reverse direction analysis suggested that genetic liability to higher educational attainment had a potential causal effect on lower risk of CUD (odds ratio (OR) [95% CI]IVW = 0.39 [0.29, 0.52], P = 1.69×10-10 ). We also found evidence of potential causal effect from genetic liability to higher educational attainment to higher risk of LCU (OR [95% CI]IVW = 1.35 [1.11, 1.66], P = 0.0033).


CONCLUSIONS
Genetic liability to cannabis use disorder (CUD) may lead to lower educational attainment. Genetic liability to higher educational attainment may also lead to higher lifetime cannabis use risk and lower CUD risk. However, the bidirectional effect between CUD and educational attainment may be due to shared risk factors (e.g., attention deficit hyperactivity disorder).