Shared genetic architecture of cortical thickness alterations in major depressive disorder and schizophrenia

被引:7
作者
Wang, He [1 ,2 ]
Zhao, Qiyu [1 ,2 ]
Zhang, Yijing [1 ,2 ]
Ma, Juanwei [1 ,2 ]
Lei, Minghuan [1 ,2 ]
Zhang, Zhihui [1 ,2 ]
Xue, Hui [1 ,2 ]
Liu, Jiawei [1 ,2 ]
Sun, Zuhao [1 ,2 ]
Xu, Jinglei [1 ,2 ]
Zhai, Ying [1 ,2 ]
Wang, Ying [1 ,2 ]
Cai, Mengjing [1 ,2 ,3 ,4 ]
Zhu, Wenshuang [1 ,2 ,5 ]
Liu, Feng [1 ,2 ]
机构
[1] Tianjin Med Univ Gen Hosp, Tianjin Key Lab Funct Imaging, Dept Radiol, 154 Anshan Rd, Tianjin 300052, Peoples R China
[2] Tianjin Med Univ Gen Hosp, Tianjin Inst Radiol, 154 Anshan Rd, Tianjin 300052, Peoples R China
[3] Henan Prov Peoples Hosp, Dept Med Imaging, Zhengzhou 450000, Peoples R China
[4] Zhengzhou Univ Peoples Hosp, Zhengzhou 450000, Peoples R China
[5] Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, Beijing 100070, Peoples R China
基金
中国国家自然科学基金;
关键词
Major depressive disorder; Schizophrenia; Cortical thickness; Gene expression; Genome-wide association studies; BDNF; PATHOPHYSIOLOGY; ABNORMALITIES; EXPRESSION; CORTEX; AREA; METAANALYSES; ASSOCIATION; PLASTICITY; PSYCHOSIS;
D O I
10.1016/j.pnpbp.2024.111121
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Major depressive disorder (MDD) and schizophrenia (SCZ) are heritable brain disorders characterized by alterations in cortical thickness. However, the shared genetic basis for cortical thickness changes in these disorders remains unclear. Methods: We conducted a systematic literature search on cortical thickness in MDD and SCZ through PubMed and Web of Science. A coordinate-based meta-analysis was performed to identify cortical thickness changes. Additionally, utilizing summary statistics from the largest genome-wide association studies for depression (Ncase = 268,615, Ncontrol = 667,123) and SCZ (Ncase = 53,386, Ncontrol = 77,258), we explored shared genomic loci using conjunctional false discovery rate (conjFDR) analysis. Transcriptome-neuroimaging association analysis was then employed to identify shared genes associated with cortical thickness alterations, and enrichment analysis was finally carried out to elucidate the biological significance of these genes. Results: Our search yielded 34 MDD (Ncase = 1621, Ncontrol = 1507) and 19 SCZ (Ncase = 1170, Ncontrol = 1043) neuroimaging studies for cortical thickness meta-analysis. Specific alterations in the left supplementary motor area were observed in MDD, while SCZ exhibited widespread reductions in various brain regions, particularly in the frontal and temporal areas. The conjFDR approach identified 357 genomic loci jointly associated with MDD and SCZ. Within these loci, 55 genes were found to be associated with cortical thickness alterations in both disorders. Enrichment analysis revealed their involvement in nervous system development, apoptosis, and cell communication. Conclusion: This study revealed the shared genetic architecture underlying cortical thickness alterations in MDD and SCZ, providing insights into common neurobiological pathways. The identified genes and pathways may serve as potential transdiagnostic markers, informing precision medicine approaches in psychiatric care.
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页数:11
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