Three genes at chromosome 3p22.3 (CRTAP, GLB1, and TMPPE) were significantly associated with mMDD after Bonferroni correction (Supplementary Table 12). Whilst CRTAP and GLB1 have not previously shown association with psychiatric disorders, both genes are members of the CNTN1 PPI subnetwork. This subnetwork contains CNTN1, which encodes a protein that may play a role in the formation of axon connections in the developing nervous system61. Furthermore, the CNTN1 PPI subnetwork also contains HTR1A, which encodes a serotonin (5-HT) receptor subtype that binds endogenous 5-HT62. To assess whether significant association of these 3 genes was due to LD in the region, the meta-analysis of MDD in males was re-run conditional on SNPs with an R2 > 0.9 with the top ranking SNP, rs4478037. This analysis, implemented in GCTA (v1.25)34, indicated that the signal was being driven by LD across the region (Supplementary Figure 5). There were no significant gene-based associations with MDD, rMDD or fMDD.
