The gender-specific association of EHD3 polymorphisms with major depressive disorder

Recent work suggests that women have a higher liability to major depressive disorder (MDD) than men, but the mechanism for the gender difference remains unknown. Given a genetic component involved in MDD, genome-wide association studies (GWAS) have been performed to search for susceptibility loci for the diseases and several genes of interest have been reported, including the EH-domain containing 3 (EHD3) gene that encodes a protein participating in endosome protein trafficking. However, the polymorphism association of the EHD3 gene with MDD failed to be replicated in a Chinese Han population. In the present study, we stratified 517 MDD patients and 455 control subjects by gender and symptoms and found 3 SNPs present in the EHD3 gene, of which rs619002 and rs644926 were exclusively associated with female MDD (p=0.0045 and p=0.0074, respectively) and rs649729 (p=0.0029) was closely related to anxious mood of female patients, suggesting a gender-specific role of EHD3 in MDD. These positive findings help explain, at least from one aspect, the poor replication of GWAS results. Further functional analysis is needed to clarify how variants in EHD3 may play a female-specific role in the pathogenesis of MDD.