Influence of TMX2-CTNND1 polymorphism on cortical thickness in schizophrenia and their unaffected sibling: an exploratory study based on target region sequencing.

Abstract

The advancement of neuroimaging and genetic research has revealed the presence of morphological abnormalities and numerous risk genes, along with their associations. The cortical thickness of 129 schizophrenia patients, 42 unaffected siblings of patients and 112 healthy controls was measured, and the candidate genes were sequenced. Comparisons of cortical thickness (including 68 regions of Desikan-Kiliany atlas) and genetic variants (within 108 risk genes for schizophrenia) among the three groups were made, and correlation analyses were performed between cortical thickness, clinical symptoms, cognitive tests like N-back and logical memory test and genetic variants. The study revealed that schizophrenia patients had significantly thinner bilateral frontal, temporal, and parietal gyrus compared to healthy controls and unaffected siblings. Furthermore, association analyses in target genes found 4 SNVs were significantly associated with schizophrenia diagnosis, including TMX2-CTNND1 (SNV20673) (PFDR = 0.008) and CENPM (rs35542507, rs41277477, rs73165153) (PFDR = 0.030). Additionally, cortical thickness in right pars triangularis was observed to be thinner in carriers of the SNV20673 variant compared to non-carriers (PFDR = 0.048). Lastly, a positive correlation was found between right pars triangularis cortical thickness and logical memory in schizophrenia patients (r = 0.199, p = 0.032). This study identified regional morphological abnormalities in schizophrenia, including the right homologue of Broca's area, which was associated with a risk variant affecting delta-1 catenin and affected logical memory. These findings suggest a potential association between candidate gene loci, cortical thickness, and schizophrenia.