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.

皮层下大脑结构与发育、精神和神经系统疾病有关。在这里，我们对 74,898 名欧洲血统参与者的颅内和 9 个皮质下脑体积（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）进行了全基因组关联研究荟萃分析。我们确定了 254 个与这些脑体积相关的独立基因座，解释了高达 35% 的表型变异。我们观察到不同分化时间点特定神经细胞类型的基因表达，包括参与细胞内信号传导和脑衰老相关过程的基因。当应用于不同血统的个体时，脑体积的多基因评分显示出预测能力。我们观察到帕金森病和注意力缺陷/多动障碍的脑容量的因果遗传效应。研究结果表明，大脑发育中的特定基因表达模式和共病神经精神疾病中的遗传变异，这可能指向与脑疾病有关的风险基因的大脑基质和作用区域。