SNPs may be functional in exerting their effects on disease phenotype if the variant either 1) substitutes an amino acid and changes protein structure (Cargill et al., 1999; Sunyaev, Ramensky, & Bork, 2000), 2) alters mRNA expression, stability or localization through regulating transcription (e.g. disrupt transcription factor binding sites at intronic enhancer or promoter regions (Prokunina et al., 2002)) or via alternate splicing (e.g. affecting exonic splicing enhancers or silencers (Cartegni, Chew, & Krainer, 2002)), or 3) if the variant is in linkage disequilibrium with another functional SNP. There are two known SNPs within the CNR1 coding region, i.e. rs1049353 (which we examined in this study) and rs3505747. However, both SNPs are synonymous variants that do not result in amino acid substitution or protein structure alterations. In our study, we did not find significant rs1049353 genotype effects on MRI brain volumes or on marijuana misuse among schizophrenia patients.
