Effects of rs2738880 Genotype on Symptom-Associated White Matter Networks in Schizophrenia: A Computational Connectomics Study

OBJECTIVE: The Disrupted-in-Schizophrenia 1 (DISC1) gene is a well-established genetic risk factor for schizophrenia (SCZ) and has been implicated in the pathogenesis of abnormal white matter (WM) development in this disorder. rs2738880, a common single-nucleotide polymorphism (SNP) within DISC1, has been linked to a spectrum of neurobiological alterations in SCZ. However, its specific impact on WM network in SCZ remains unclear. This study utilized magnetic resonance imaging and genotyping to investigate these mechanisms. METHODS: We recruited 332 Han Chinese participants, used magnetic resonance imaging scanning to assess WM integrity, and constructed a WM network for each individual. Besides that, we used imLDRTM SNP typing technology to determine the genotypes of SNPs at rs2738880. Furthermore, we used two-way analysis of covariance and partial correlation analysis (gender and age as covariates) to investigate the effects of rs2738880. RESULTS: While no significant main effects of genotype were observed, a significant diagnosis×genotype interaction on network local efficiency (Elocal) was identified (F(1,190)=7.353, p=0.007, η2p=0.037). Post-hoc tests revealed that patients carrying the G allele (AG/GG genotypes) exhibited significantly lower Elocal compared to other groups. Furthermore, Elocal was negatively correlated with symptom severity in the patient group (r=-0.194, p=0.038). CONCLUSION: Our study suggests that the DISC1 rs2738880 G allele might be associated with network vulnerability and symptom severity in SCZ. However, the biological pathways through which the G allele influences WM network properties warrant further investigation.