containing nAChRs, could affect dopamine release, a known neurotransmitter involved in addiction. 3) There could be a strong biological link between expression of CHRNA2 and the cannabinoid receptor 1 gene (CNR1). This hypothesis is based on evaluation of gene-expression correlations from genome-wide microarray gene expression profiles in the Allan Brain Atlas (http://www.brain-map.org/). We found that of all genes evaluated (58,692 probes analyzed), CNR1 demonstrated the strongest negative correlation with CHRNA2 expression (rmax=−0.498; Supplementary Figure 4). The signal was driven by opposite expression patterns in a large number of brain tissues, e.g in cerebellum where CNR1 had a relatively high expression in the cerebellar cortex and CHRNA2 had a relatively low expression and the opposite was observed for cerebellar nuclei (Supplementary Figure 4). This suggests the existence of a currently uncharacterized biological interaction between the endocannabinoid system and alpha-2 subunit containing nAChRs, by which the identified risk locus which is associated with decreased CHRNA2 expression could be related to increased CNR1 expression.
