Context: Individual differences exist in sensitivity to the psychotomimetic effect of cannabis; the molecular genetic basis underlying differential sensitivity remains elusive. Objective: To investigate whether selected schizophrenia candidate single-nucleotide polymorphisms (SNPs) moderate effects of cannabis use. Design: Interactions between recent cannabis use, determined by urinalysis results, and 152 SNPs in 42 candidate genes were examined in 740 unaffected siblings of 801 patients with

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... ychosis to examine genetic moderation of the association between Structured Interview for Schizotypy-Revised positive schizotypy and recent cannabis use (at-risk paradigm). The SNPs showing Bonferroni-adjusted association in the at-risk paradigm were used in a case-only analysis in the 801 patients, as well as in a case-sibling and case-control analysis (using 419 controls) focusing on genetic moderation of developmental effects of cannabis on later psychotic disorder. Setting: The Netherlands and Flanders, Belgium. Participants: Eight hundred one patients with psychosis and their 740 unaffected siblings. Main Outcome Measure: Significant interaction between any of the selected SNPs and cannabis in the at-risk paradigm, followed by selective case-only, casesibling, and case-control analyses.