as potential drug targets for MDD.38 GAL also has an important role in the hippocampal processing of cognition.39 Our most associated SNP in GAL (rs2156464, P=2.7 × 10−5, OR=1.24, CI=1.12–1.37, MAF=0.19) lies in the same haplotype block as an association reported for panic disorder.40 Another top ranked gene (ADCY3) encodes the enzyme adenylate cyclase 3 that catalyses synthesis of cyclic adenosine monophosphate, the association underpinned by SNP rs2384061 (P=6.3 × 10−6, OR=1.20, CI=1.11–1.29, MAF=0.42, Table 3). ADCY3 is an plausible candidate gene because depressed patients display reduction in platelet ADCY activity.41 Perhaps most interesting is that ADCY and GAL activity are inter-related42 and ADCY3 binds CACNA1C (calcium channel, voltage dependent, L type, α-1C subunit).43 A SNP (rs1006737, intron 3) within the gene CACNA1C is associated with bipolar disorder44 schizophrenia and MDD.45 In this study, CACNA1C ranked in the top 4% of genes and we replicated the association with rs1006737 (P=0.020, OR=1.10, CI=1.01–1.19, MAF=0.34), but the top associated SNP in CACNA1C was rs98545 (P=0.0019, OR=0.83, CI 0.75–0.94, MAF=0.15, intron 29). rs98545 lies 387 kb from rs1006737; they are in near linkage equilibrium (r2=0.06) and in our data their effects are additive in a logistic regression. Neither rs1006737 nor rs98545 were genotyped
