Genetic variations in DOCK4 contribute to schizophrenia susceptibility in a Chinese cohort: A genetic neuroimaging study

• Published in: Behavioural brain research Vol. 443; p. 114353
• Main Authors: Xu, Xusan, He, Bin, Zeng, Jieqing, Yin, Jingwen, Wang, Xiaoxia, Luo, Xudong, Liang, Chunmei, Luo, Shucun, Yan, Haifeng, Xiong, Susu, Tan, Zhi, Lv, Dong, Dai, Zhun, Lin, Zhixiong, Lin, Juda, Ye, Xiaoqing, Chen, Riling, Li, You, Wang, Yajun, Chen, Wubiao, Luo, Zebin, Li, Keshen, Ma, Guoda
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 12.04.2023
• Subjects: DOCK4; East Asian People; Functional connectivity; Genetic association; Genetic Variation; GTPase-Activating Proteins - genetics; Humans; Magnetic Resonance Imaging - methods; Neuroimaging; Polymorphism, Single Nucleotide; Schizophrenia; Schizophrenia - genetics; Single nucleotide polymorphisms; Functional connectivity; Schizophrenia; DOCK4; Single nucleotide polymorphisms; Genetic association
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2023.114353

Emerging evidence suggests that the DOCK4 gene increases susceptibility to schizophrenia. However, no study has hitherto repeated this association in Chinese, and further investigated the relationship between DOCK4 and clinical symptoms in schizophrenic patients using clinical scales and functional magnetic resonance imaging (fMRI). In this study, we genotyped three single nucleotide polymorphisms (SNPs) (rs2074127, rs2217262, and rs2074130) within the DOCK4 gene using a case-control design (including 1289 healthy controls and 1351 patients with schizophrenia). 55 first-episode schizophrenia (FES) patients and 59 healthy participants were divided by the genotypes of rs2074130 into CC and CT+TT groups. We further investigated the association with clinical symptoms and neural characteristics (brain activation/connectivity and nodal network metrics). Our results showed significant associations between all selected SNPs and schizophrenia (all P < 0.05). In patients, letter fluency and motor speed scores of T allele carriers were significantly higher than the CC group (all P < 0.05). Interestingly, greater brain activity, functional connectivity, and betweenness centrality (BC) in language processing and motor coordination were also observed in the corresponding brain zones in patients with the T allele based on a two-way ANCOVA model. Moreover, a potential positive correlation was found between brain activity/connectivity of these brain regions and verbal fluency and motor speed. Our findings suggest that the DOCK4 gene may contribute to the onset of schizophrenia and lead to language processing and motor coordination dysfunction in this patient population from China.