The limitations of this study include our relatively small sample of patients with marijuana misuse and absence of comparison groups. Future studies will need to include healthy controls and marijuana abusers without schizophrenia in order to determine the specificity of the effects of CNR1 gene polymorphisms on brain structure and function. Furthermore, our statistical analyses used FDR to adjust for multiple comparisons. Although FDR-controlling methods yield greater statistical power, these are less stringent than Bonferroni-correction or familywise error rate controlling methods. We chose a two-step analytic approach to limit Type I errors in order to explore the influence of CNR1 on carefully selected phenotypic measures. No prior studies have genotyped CNR1 to this level of genomic coverage in relation to phenotypic features of schizophrenia. Nonetheless, our findings of genotype-phenotype associations are preliminary and will require future replication. There is often substantial co-occurrence of alcohol and other illicit drug use among individuals with marijuana abuse/dependence. Even though our study sample is representative of this population, comorbid alcohol and non-marijuana substance misuse remains as a potential confounding factor in genotype-phenotype associations despite
