With the exception of polygenic profiling analysis, MDD in males generally did not conform to the pattern of results demonstrated by other MDD definitions. Some of these differences, such near-zero SNP-based heritability estimate and subsequently no genetic correlations with other traits surviving multiple testing correction, can be attributed to reduced statistical power in this MDD definition. Interestingly, genome-wide meta-analysis yielded a single genome-wide significant locus in depression in males. The locus at chromosome 3p22.3 includes TMPPE, CRTAP, and GLB1 genes; all of which were significant in gene-based testing. Conditional GWAS on the lead signal demonstrated that the signal which spanned these three genes was due to high LD in the region. However, functional genomic analysis of the lead SNP returned eQTL evidence for GLB1 and CRTAP, suggesting that the causal variant is more likely to affect the expression of these genes rather than TMPPE. The lack of replication of this signal in other published GWAS is unfortunate, but unsurprising given that the current study is the largest GWAS of depression in males to date (relative to published GWAS). Ever-increasing sample
