ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Schizophrenia
Effects of rs2738880 Genotype on Symptom-Associated White Matter Networks in Schizophrenia: A DTI Connectomics Study
Provisionally accepted
- 1School of Psychology, Shandong Second Medical University, Weifang, China
- 2School of Information Engineering, Weifang Vocational College, Weifang, China
- 3School of Clinical Medicine, Shandong Second Medical University, Weifang, China
- 4Departments of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
- 5Weifang Mental Health Centre, Weifang, China
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ABSTRACT Introduction: The Disrupted-in-Schizophrenia 1 (DISC1) gene is a well-established genetic risk factor for schizophrenia and has been implicated in the pathogenesis of abnormal white matter development in this disorder. rs2738880, a common SNP within DISC1, has been linked to a spectrum of neurobiological alterations in schizophrenia. However, its specific impact on white matter network in schizophrenia remains unclear. This study utilized magnetic resonance imaging and genotyping to investigate these mechanisms. Methods: We recruited 332 Han Chinese participants, used DTI scanning to assess white matter integrity, and constructed a white matter 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 ANCOVA and partial correlation analysis (disease duration, 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 = 7.353, P = 0.007). Post-hoc tests revealed that patients carrying the G allele (GG/GA 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). Conclusions: Our findings suggest that the DISC1 rs2738880 G allele may compromise the compensatory capacity of white matter networks in schizophrenia, thereby elevating disease risk and symptom severity. Future multimodal data will be instrumental in further validating and elucidating this phenomenon.
Keywords: DISC1 gene, network local efficiency, rs2738880, Schizophrenia, white matter network
Received: 07 Oct 2025; Accepted: 29 Dec 2025.
Copyright: © 2025 Wang, Gao, Gao, Meng, Li and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shuai Wang
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