To assess brain volume-CNR1 relationships, statistical analyses were conducted in stages to reduce Type I error. We first tested whether there was an overall effect of each CNR1 genotype (minor allele carriers versus major allele homozygotes) on total cerebral GM or on total cerebral WM volumes. We used the adaptive false discovery rate (FDR) (Benjamini & Hochberg, 2000) procedure to control for potential type I error rate inflation due to multiple testing. Compared to familywise error rate controlling methods, FDR-controlling methods generally provide greater statistical power (Sabatti, Service, & Freimer, 2003). In each general linear model, total cerebral brain volume was entered as dependent measure, and genotype the independent variable. As a second step, for CNR1 genotypes in which the total cerebral brain volume test was statistically significant (FDR-adjusted p≤.05), follow-up analyses were performed to determine differential brain volume-CNR1 relationships across patients with versus patients without marijuana abuse/dependence. In each follow-up ANCOVA, the dependent variable was frontal, temporal or parietal lobar brain volume. Genotype, marijuana misuse (presence versus absence of lifetime marijuana abuse or dependence) and genotype-by-marijuana misuse interaction terms
