TESC gene-regulating genetic variant (rs7294919) affects hippocampal subfield volumes and parahippocampal cingulum white matter integrity in major depressive disorder

Two recent genome-wide association studies have suggested that rs7294919 is associated with changes in hippocampal volume. rs7294919 regulates the transcriptional products of the TESC gene, which is involved in neuronal proliferation and differentiation. We investigated the interactive effect of rs7294919 and major depressive disorder (MDD) on the volume of the hippocampal subfields and the integrity of the parahippocampal cingulum (PHC). We also investigated the correlation of these structural changes with the DNA methylation status of rs7294919. A total of 105 patients with MDD and 85 healthy control subjects underwent T1-weighted structural magnetic resonance imaging and diffusion tensor imaging. The rs7294919 was genotyped and its DNA methylation status was assessed in all the participants. We analyzed the hippocampal subfield volumes and PHC integrity using FreeSurfer and the Tracts Constrained by Underlying Anatomy (TRACULA) respectively. Significant interactive effects of rs7294919 and MDD were observed in the volumes of the dentate gyrus and CA4. The patients with MDD had increased methylation in two of the three CpG loci of rs7294919, and the methylation of CpG3 was significantly correlated with right PHC integrity in the MDD group. Our results provide neurobiological evidence for the association of rs7294919 with brain structural changes in MDD.