Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus

This is supplementary data for the manuscript, "Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus". Abstract: Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n=399, dorsolateral prefrontal cortex: n=377, and hippocampus: n=394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.本数据集为论文《性别通过背外侧前额叶皮层（dorsolateral prefrontal cortex）、海马体（hippocampus）及尾状核（caudate nucleus）影响精神分裂症的转录关联》的补充数据集。 摘要：精神分裂症是一种复杂的神经精神疾病，具有性别二态性特征，包括症状表现、药物反应性及发病率的性别差异，其中男性发病率更高。此前针对精神分裂症性别差异的大规模转录组分析，多聚焦于前额叶皮层。本研究分析了脑序列联盟（BrainSeq Consortium）的数据集：尾状核（caudate nucleus）样本量n=399、背外侧前额叶皮层（dorsolateral prefrontal cortex）样本量n=377、海马体（hippocampus）样本量n=394，共鉴定出831个在多个脑区呈现性别差异的独特基因，这些基因显著富集于免疫相关通路。我们观察到，精神分裂症男性患者的海马体中存在X染色体剂量降低现象。本研究的性别交互模型显示，有148个剪接位点在精神分裂症中呈现性别特异性失调。针对精神分裂症的性别特异性分析鉴定出数十个差异表达基因，此类基因同样显著富集于免疫相关通路。最后，我们的性别交互表达数量性状基因座（expression quantitative trait loci, eQTL）分析鉴定出704个独特基因，其中9个与精神分裂症风险相关。本研究结果凸显了针对性别二态性特征开展基于性别的分析的重要性，可为精神分裂症的个性化治疗策略提供参考，并强调了精神分裂症研究中需扩大女性样本量的必要性。