澳大利亚昆士兰大学Miguel E. Rentería小组发现，颅内和皮层下脑体积的基因组分析产生涉及到不同血统变异的多基因评分。相关论文于2024年10月21日在线发表在《自然—遗传学》杂志上。

研究人员对74898名欧洲血统参与者进行颅内和九个皮层下脑体积（脑干、尾状核、壳核、海马、苍白球、丘脑、伏隔核、杏仁核和腹侧间脑）的全基因组关联研究元分析。研究人员识别了254个与这些脑体积相关的独立位点，解释了多达35%的表型变异。

研究人员观察到特定神经细胞类型在不同分化时间点的基因表达，包括参与细胞内信号传导和与脑衰老相关的过程的基因。脑体积的多基因评分在不同血统个体中显示出预测能力。研究人员还观察到脑体积与帕金森病和注意缺陷/多动障碍的因果遗传效应。

这些研究结果揭示了脑发育中特定的基因表达模式和共病神经精神疾病中的遗传变异，可能指向与脑疾病相关的风险基因的脑基质和作用区域。

据悉，皮层下脑结构参与发育、精神和神经疾病的发生。

附：英文原文

Title: Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Author: Garca-Marn, Luis M., Campos, Adrian I., Diaz-Torres, Santiago, Rabinowitz, Jill A., Ceja, Zuriel, Mitchell, Brittany L., Grasby, Katrina L., Thorp, Jackson G., Agartz, Ingrid, Alhusaini, Saud, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arfanakis, Konstantinos, Arias-Vasquez, Alejandro, Armstrong, Nicola J., Athanasiu, Lavinia, Bastin, Mark E., Beiser, Alexa S., Bennett, David A., Bis, Joshua C., Boks, Marco P. M., Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Burkhardt, Ralph, Cahn, Wiepke, Calhoun, Vince D., Carmichael, Owen T., Chakravarty, Mallar, Chen, Qiang, Ching, Christopher R. K., Cichon, Sven, Crespo-Facorro, Benedicto, Crivello, Fabrice, Dale, Anders M., Smith, George Davey, de Geus, Eco J. C., De Jager, Philip L., de Zubicaray, Greig I., Debette, Stphanie, DeCarli, Charles, Depondt, Chantal, Desrivires, Sylvane, Djurovic, Srdjan, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fernndez, Guilln, Filippi, Irina, Fisher, Simon E., Fleischman, Debra A., Fletcher, Evan, Fornage, Myriam, Forstner, Andreas J., Francks, Clyde, Franke, Barbara

Issue&Volume: 2024-10-21

Abstract: Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson’s disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.

DOI: 10.1038/s41588-024-01951-z

Source: https://www.nature.com/articles/s41588-024-01951-z