Yao Shuyang, Harder Arvid, Darki Fahimeh, Chang Yu-Wei, Li Ang, Nikouei Kasra, Volpe Giovanni, Lundström Johan N, Zeng Jian, Wray Naomi R, Lu Yi, Sullivan Patrick F, Hjerling-Leffler Jens
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Nat Commun. 2025 Jan 4;16(1):395. doi: 10.1038/s41467-024-55611-1.
Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability. Using functional MRI connectivity, we further confirmed the significance of the central and lateral amygdala, hippocampal body, and prefrontal cortex in distinguishing schizophrenia cases from controls. Our findings underscore the value of single-cell transcriptomics in understanding the polygenicity of psychiatric disorders and suggest a promising alignment of genomic, transcriptomic, and brain imaging modalities for identifying common biological targets.
识别对精神疾病和大脑特征至关重要的细胞类型和脑区对于有针对性的神经生物学研究至关重要。通过将全基因组关联研究的基因组见解与成人人脑的综合单细胞转录组图谱相结合，我们对特定的神经元簇进行了优先级排序，这些神经元簇在精神分裂症、双相情感障碍和重度抑郁症以及智力、教育和神经质的单核苷酸多态性（SNP）遗传力方面显著富集。将细胞类型结果外推到脑区揭示了精神分裂症遗传风险对全脑的影响，海马体和杏仁核的子区域表现出最显著的SNP遗传力富集。使用功能磁共振成像连接性，我们进一步证实了中央和外侧杏仁核、海马体主体和前额叶皮质在区分精神分裂症患者与对照组中的重要性。我们的研究结果强调了单细胞转录组学在理解精神疾病多基因性方面的价值，并为识别共同生物学靶点的基因组、转录组和脑成像模式提供了有前景的整合方向。
