Division of Psychiatry Research, The Zucker Hillside Hospital, Northwell, Glen Oaks, NY, USA.
Institute of Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Nat Commun. 2022 Nov 11;13(1):6868. doi: 10.1038/s41467-022-34418-y.
Cognitive deficits are known to be related to most forms of psychopathology. Here, we perform local genetic correlation analysis as a means of identifying independent segments of the genome that show biologically interpretable pleiotropic associations between cognitive dimensions and psychopathology. We identify collective segments of the genome, which we call "meta-loci", showing differential pleiotropic patterns for psychopathology relative to either cognitive task performance (CTP) or performance on a non-cognitive factor (NCF) derived from educational attainment. We observe that neurodevelopmental gene sets expressed during the prenatal-early childhood period predominate in CTP-relevant meta-loci, while post-natal gene sets are more involved in NCF-relevant meta-loci. Further, we demonstrate that neurodevelopmental gene sets are dissociable across CTP meta-loci with respect to their spatial distribution across the brain. Additionally, we find that GABA-ergic, cholinergic, and glutamatergic genes drive pleiotropic relationships within dissociable meta-loci.
认知缺陷与大多数形式的精神病理学有关。在这里，我们进行局部遗传相关性分析，以确定基因组中具有生物学可解释的认知维度与精神病理学之间的可分的、多效性关联的独立片段。我们确定了“元位置”的集体基因组片段，这些片段相对于认知任务表现（CTP）或从教育程度得出的非认知因素（NCF），显示出与精神病理学的不同多效性模式。我们观察到，在与 CTP 相关的元位置中，主要是在产前-幼儿期表达的神经发育基因集，而出生后基因集更多地参与与 NCF 相关的元位置。此外，我们证明，神经发育基因集在 CTP 元位置上是可分离的，这与其在大脑中的空间分布有关。此外，我们发现 GABA 能、胆碱能和谷氨酸能基因在可分离的元位置内驱动多效性关系。
