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

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.

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.

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).

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.