The primary finding of this paper is that no locus reached genome-wide significance in the combined discovery and replication analysis of MDD. Our results are consistent with null results from other MDD meta-analyses using subsets of the present sample.22,23,25,28 The risk profile analyses are consistent with the presence of genetic effects, which our analysis was underpowered to detect. Although not significant, several analyses (that is, MDD, femalesonly and recurrent MDD) pointed at a region on chr3:185.3Mb near the gene (DVL3) encoding the Wnt-signaling phosphoprotein disheveled 3. DVL3 transcripts are decreased in the nucleus accumbens of individuals with MDD71 and are overexpressed in the leukocytes of individuals reporting social isolation,72 and the DVL3 protein product is upregulated in rats after treatment with antipsychotics.73,74 The chr3:185.3 Mb region also contains several serotonin receptors (HTR3D, HTR3C and HTR3E). However, none of these analyses were strongly compelling.
