Data from the Adolescent Brain Cognitive Development Study (Registered; ABCD study)43 (data release 2.0.1) were used to test the association of PRS for cannabis use disorder with brain structure among 4539 cannabis-naive children (through self-reporting or hair toxicology) of European ancestry (mean age 9·93 years [SD 0·63], 2125 [47%] were girls; appendix p 17). Total bilateral white matter volume, grey matter volume, and intracranial volume were estimated using FreeSurfer 5.3.44 PRS from the cannabis use disorder GWAS were generated at nine p value thresholds (ie, p<0·0001, p<0·001, p<0·01, p<0·10, p<0·20, p<0·30, p<0·40, p<0·50, and p<1·00), as were PRS for cannabis use.5 Linear mixed models were used to include scanner (for imaging analyses) and family as nested random effects, done using the lme4 package in R, version 3.6.0. All analyses included as fixed effect covariates the first 20 ancestral principal components, age, sex, age by sex, parents combined income, caregiver education, genotyping batch, caregiver's marital status, prenatal cannabis exposure before and after knowledge of pregnancy, and twin status. Multiple testing within each brain structure phenotype was accounted for by applying random
