The PRS for cannabis use disorder were significantly associated with reduced total white matter volume in cannabis-naive children from the ABCD Study (standardised β=–0·04; p=0·001; figure 4), explaining up to 0·18% of the variance in white matter volume at the most predictive threshold of p<0·5 (appendix p 18). Children in the highest quartile of PRS, on average, had a white matter volume that was 1% lower than those in the lowest quartile. Results remained significant when including intracranial volume as a covariate (standardised β=–0·08, p=0·01) and when excluding 1246 (27%) of 4539 children who used any substance (standardised β=–0·05, p=0·001), or when excluding 2482 (54%) of 4539 who used any substance or were prenatally exposed to any substance (standardised β=–0·05, p=0·03). The PRS for cannabis use were not significantly correlated with white matter volume (figure 3). After correction for multiple testing, there was no association between PRS for cannabis use disorder or cannabis use and grey matter volume (all p>0·01; appendix p 18, 31).
