altered CNR1 Exon 3 RNA levels in the human brain (Zhang et al., 2004) as well as with prefrontal CB1 receptor expression differences (Hutchison et al., 2008). Thus, phenotypic abnormalities associated with rs9450898 observed in the current study may be related to LD with known functional variants, or to yet unknown direct effects of rs9450898 on altering transcriptional regulation. The genomic sequence surrounding rs12720071 (i.e. GATTC) may be a potential transcription factor binding site (Heinemeyer et al., 1998). Presence of the A-allele on rs12720071 predicts a transcription factor binding site for CCAAT/enhancer-binding protein beta (C/EBPbeta)(Akira et al., 1990). C/EBPbeta is a member of the transcription factor family comprising of basic leucine-zipper DNA-binding proteins that recognizes a common DNA-binding sequence (Vinson, Sigler, & McKnight, 1989). These C/EBP transcription factors can promote or repress gene expression to regulate embryonic neurogenesis, adult neuroplasticity, learning/memory and neuronal regeneration following injury (Alberini, Ghirardi, Metz, & Kandel, 1994; Cortes-Canteli, Pignatelli, Santos, & Perez-Castillo, 2002; Menard et al., 2002; Sterneck & Johnson, 1998; Taubenfeld, Milekic, Monti, & Alberini, 2001). Thus, the A>G substitution on rs12720071 may potentially disrupt C/EBPbeta transcription factor binding, and leads to WM volume deficits and cognitive dysfunction among rs12720071-G-alleles carriers with heavy marijuana
