Liao Zhijie, Kumar Kuldeep, Kopal Jakub, Huguet Guillaume, Saci Zohra, Jean-Louis Martineau, Pausova Zdenka, Jurisica Igor, Bearden Carrie E, Jacquemont Sebastien, Paus Tomas
Centre de Recherche du CHU Sainte-Justine, Montreal, QC, Canada.
Departments of Psychiatry and Addictology, University of Montreal, Montreal, QC, Canada.
Nat Commun. 2025 Feb 17;16(1):1697. doi: 10.1038/s41467-025-56855-1.
The tangential expansion of the human cerebral cortex, indexed by its surface area (SA), occurs mainly during prenatal and early postnatal periods, and is influenced by genetic factors. Here we investigate the role of rare copy number variants (CNVs) in shaping SA, and the underlying mechanisms, by aggregating CNVs across the genome in community-based cohorts (N = 39,015). We reveal that genome-wide CNV deletions and duplications are associated with smaller SA. Subsequent analyses with gene expression in fetal cortex suggest that CNVs influence SA by interrupting the proliferation of neural progenitor cells during fetal development. Notably, the deletion of genes with strong (but not weak) coexpression with neural progenitor genes is associated with smaller SA. Follow up analyses reveal similar mechanisms at play in three clinical CNVs, 1q21.1, 16p11.2 and 22q11.2. Together, this study of rare CNVs expands our knowledge about genetic architecture of human cerebral cortex.
以表面积（SA）为指标的人类大脑皮质的切向扩展主要发生在产前和产后早期，并受遗传因素影响。在此，我们通过在基于社区的队列（N = 39,015）中汇总全基因组的拷贝数变异（CNV），研究罕见拷贝数变异在塑造SA中的作用及其潜在机制。我们发现全基因组CNV缺失和重复与较小的SA相关。随后对胎儿皮质基因表达的分析表明，CNV通过在胎儿发育过程中干扰神经祖细胞的增殖来影响SA。值得注意的是，与神经祖基因有强（而非弱）共表达的基因缺失与较小的SA相关。后续分析揭示了在三个临床CNV（1q21.1、16p11.2和22q11.2）中也存在类似机制。总之，这项关于罕见CNV的研究扩展了我们对人类大脑皮质遗传结构的认识。
