Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1–C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development. Autism spectrum disorder and schizophrenia were specifically associated with C1/C2 and C3, respectively, across neuroimaging, differential expression and genome-wide association studies. Evidence converged especially in support of C3 as a normative transcriptional program for adolescent brain development, which can lead to atypical supragranular cortical connectivity in people at high genetic risk for schizophrenia.

人脑组织涉及数千个基因的协调表达。例如，皮质转录的第一主成分（C1）识别从感觉运动到关联区域的层次结构。在这项研究中，艾伦人脑图谱的优化处理揭示了皮质基因表达结构的两个新组成部分，C2和C3，它们在神经元、代谢和免疫过程、特定细胞类型和细胞结构以及与智力相关的遗传变异方面明显丰富。使用其他数据集（PsychENCODE、Allen Cell Atlas 和 BrainSpan），我们发现 C1-C3 代表通用转录程序，这些程序在细胞内协调，并在胎儿和出生后发育过程中处于不同阶段。在神经影像学、差异表达和全基因组关联研究中，自闭症谱系障碍和精神分裂症分别与 C1/C2 和 C3 特别相关。证据集中，尤其支持 C3 作为青少年大脑发育的规范转录程序，这可能导致精神分裂症高遗传风险人群出现非典型的颗粒上皮层连接。