To determine whether any genes harbored an excess of low-associated variants, we undertook gene-based tests which account for both gene length and linkage disequilibrium between SNPs. Our top associated genes were not replicated in the gene-based test when applied to the GAIN–MDD or UK MDD results, although some genes retained low association P-values when applied to the meta-analysis results (Table 4). Despite this there are some suggestive results worthy of note. Among the top ranked genes is GAL, which encodes the neuropeptide galanin, proposed by Weiss et al.36 as having an important role in MDD. Their hypothesis, based on animal models is that GAL released in the ventral tegmentum inhibits the activity of dopaminergic cells resulting in decreased motor activity and anhedonia. GAL is a regulator of brain serotonin and 5-HT1A receptor-mediated transmission,37 agonists of GAL receptors have been proposed 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
