Abstract
Schizophrenia stands out as one of the most devastating psychiatric disorders. Previous findings have shown that schizophrenia is a polygenic genetic disorder. Thus, abnormal neurodevelopment and neurogenesis may be associated with the etiology of schizophrenia, so genes which affect these processes may be potential candidate genes of schizophrenia. Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) gene is a member of the mitogen-activated protein kinase family. Taking into account previous findings, MAP3K4 plays a crucial role in the fundamental pathology of various nervous system diseases. In the present study, we aim to explore the association of MAP3K4 and schizophrenia in an independent case-control sample including 627 schizophrenic patients and 1175 healthy controls from a Northeast Chinese Han population. Both the allelic and genotypic association analyses showed that 6 SNPs in MAP3K4 were significantly associated with schizophrenia (rs590988, rs625977, rs9295134, rs12110787, rs1001808 and rs9355870). After rigorous Bonferroni correction, 4 SNPs (rs9295134, rs12110787, rs1001808 and rs9355870) were still significantly associated with the disease. The haplotype composed of these four SNPs also showed significantly global and individual association with schizophrenia. These results suggest that MAP3K4 is a susceptibility gene for schizophrenia in the Northeast Chinese Han population.
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Acknowledgements
We extend our gratitude to all the patients participating in this study. This work was supported by Education Department of Liaoning Province, China LZ2020023 (to Z.L.), and the Dalian Young Star of Science and Technology 2019RQ116 (to Z.L.). We are also grateful for the support from Liaoning BaiQianWan Talents Program.
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Zhi-Lin Luan contributed to the conception of the study, designed the experiments, and revised the manuscript. Yang Sun performed the experiments and analyzed the data. Ye Lv performed the experiments and drafted the original manuscript. Hui-Wen Ren revised the manuscript. Guan-Yu Wang analyzed the data. Li-Na Xuan performed the experiments. Yi-Yang Luo performed the experiments. All the authors reviewed and approved this manuscript.
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This study was approved by the Ethical Committee of Dalian Seventh People’s Hospital (ID:2020-18).
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Yang Sun and Ye Lv contributed equally to this work.
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Sun, Y., Lv, Y., Ren, HW. et al. Association between MAP3K4 gene polymorphisms and the risk of schizophrenia susceptibility in a Northeast Chinese Han population. Metab Brain Dis 37, 1365–1371 (2022). https://doi.org/10.1007/s11011-022-00957-y
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DOI: https://doi.org/10.1007/s11011-022-00957-y