由2347种神经影像表型全基因组分析揭示了人类皮质组织和发育遗传信息，这一成果由英国剑桥大学Richard A. I. Bethlehem、Varun Warrier团队经过不懈努力而取得。相关论文于2023年8月17日发表在《自然-遗传学》杂志上。

研究人员对13种结构和扩散磁共振成像衍生的皮质表型进行了全基因组关联荟萃分析，在全球范围内测量了36，663名个体180处双边平均区域，并在实验范围确定了4，349个重要位点。这些表型包括皮质厚度、表面积、灰质体积、折叠测量、神经突触密度和水扩散。研究确定了四种潜在遗传结构以及表面积与皮质折叠之间的因果关系。这些潜在结构部分与发育过程中不同的基因表达轨迹有关，并针对不同的细胞类型富集。

研究还确定了神经发育和受限基因的差异富集，并证明与皮质扩张相关的常见遗传变异与头部畸形疾病有关。最后，研究揭示了13种表型之间复杂的表型和区域间遗传关系，反映了它们之间的发育差异。总之，这些分析确定了皮层不同遗传组织与神经发育的相关性。

据了解，人们对人大脑皮层遗传学的理解在大脑结构表型多样性和解剖粒度方面都非常有限。

附：英文原文

Title: Genetic insights into human cortical organization and development through genome-wide analyses of 2,347 neuroimaging phenotypes

Author: Warrier, Varun, Stauffer, Eva-Maria, Huang, Qin Qin, Wigdor, Emilie M., Slob, Eric A. W., Seidlitz, Jakob, Ronan, Lisa, Valk, Sofie L., Mallard, Travis T., Grotzinger, Andrew D., Romero-Garcia, Rafael, Baron-Cohen, Simon, Geschwind, Daniel H., Lancaster, Madeline A., Murray, Graham K., Gandal, Michael J., Alexander-Bloch, Aaron, Won, Hyejung, Martin, Hilary C., Bullmore, Edward T., Bethlehem, Richard A. I.

Issue&Volume: 2023-08-17

Abstract: Our understanding of the genetics of the human cerebral cortex is limited both in terms of the diversity and the anatomical granularity of brain structural phenotypes. Here we conducted a genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging-derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,663 individuals and identified 4,349 experiment-wide significant loci. These phenotypes include cortical thickness, surface area, gray matter volume, measures of folding, neurite density and water diffusion. We identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with cortical expansion are associated with cephalic disorders. Finally, we identified complex interphenotype and inter-regional genetic relationships among the 13 phenotypes, reflecting the developmental differences among them. Together, these analyses identify distinct genetic organizational principles of the cortex and their correlates with neurodevelopment.

DOI: 10.1038/s41588-023-01475-y

Source: https://www.nature.com/articles/s41588-023-01475-y