Data Sheet 1_Reported race-associated differences in control and schizophrenia post-mortem brain transcriptomes implicate stress-related and neuroimmune pathways.csv

BackgroundThe molecular mechanisms underlying racial disparities in schizophrenia (SCZ) illness courses and outcomes are poorly understood. While these differences are thought to arise partly through stressful social gradients, little is known about how these differences are reflected in the brain, nor how they might underlie disparate psychiatric outcomes.
MethodsTo better understand the neuro-molecular correlates of social gradients, SCZ, and their overlap, we analyzed post-mortem dorsolateral prefrontal cortex (DLPFC) RNAseq data from two racially diverse cohorts in the CommonMind Consortium (235 reported Black and 546 White, 322 SCZ cases and 459 controls) using differential expression and gene set variation analyses.
ResultsWe observed differences in brain gene expression that were consistent across cohorts and reported race. A combined mega-analysis identified 1,514 genes with differential expression (DE) between reported race groups after accounting for diagnosis and other covariates. Functional enrichment analyses identified upregulation of genes involved in stress and immune response, highlighting the potential role of environmental differences between reported race groups. In a race-by-diagnosis interaction analysis, no individual genes passed statistical significance. However, 109 gene sets showed statistically significant differences, implicating metabolic and immune pathways.
ConclusionOur results suggest molecular mechanisms uniquely perturbed across reported race groups and identify several candidate pathways associated with SCZ in a reported race-dependent manner. Our results underscore the importance of diverse cohort ascertainment to better capture population-level differences in SCZ pathogenesis.

研究背景
目前学界对精神分裂症（Schizophrenia, SCZ）患者病程与转归的种族差异背后的分子机制尚不清楚。尽管这类差异被认为部分源于压力性社会梯度，但学界对这些差异如何反映在大脑中，以及它们如何导致不同的精神疾病转归，仍知之甚少。

研究方法
为更好地理解社会梯度、精神分裂症及其重叠关联的神经分子相关性，本研究采用差异表达分析（differential expression analysis）与基因集变异分析（gene set variation analysis），对共同心智联盟（CommonMind Consortium）中两个种族多样化队列的死后背外侧前额叶皮层（dorsolateral prefrontal cortex, DLPFC）RNA测序（RNA-seq）数据进行分析。这两个队列共包含235名自述为黑人的个体、546名自述为白人的个体，其中322例精神分裂症患者与459名健康对照者。

研究结果
我们观察到不同队列与自述种族群体间均一致存在大脑基因表达差异。合并的大规模分析显示，在校正诊断与其他协变量后，自述种族群体间共有1514个基因存在差异表达（differential expression, DE）。功能富集分析发现，参与应激与免疫应答的基因出现上调，这凸显了自述种族群体间环境差异的潜在作用。在种族×诊断交互分析中，未发现单个基因达到统计学显著性。但有109个基因集呈现出具有统计学意义的差异，涉及代谢与免疫通路。

研究结论
本研究结果表明，自述种族群体间存在独特扰动的分子机制，并鉴定出若干以自述种族依赖方式与精神分裂症相关的候选通路。研究结果凸显了采用多样化队列招募的重要性，以便更好地捕捉精神分裂症发病机制中的人群水平差异。