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整合基因组富集分析确定了与神经性厌食症和强迫症相关的大脑区域和发育阶段。

Integrative Genomic Enrichment Analysis Identified the Brain Regions and Development Stages Related to Anorexia Nervosa and Obsessive-Compulsive Disorder.

机构信息

Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, P.R. China.

出版信息

Cereb Cortex. 2020 Nov 3;30(12):6481-6489. doi: 10.1093/cercor/bhaa214.

DOI:10.1093/cercor/bhaa214
PMID:32770201
Abstract

Our aim is to explore the spatial and temporal features of anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) considering different brain regions and development stages. The gene sets related to 16 brain regions and nine development stages were obtained from a brain spatial and temporal transcriptomic dataset. Using the genome-wide association study data, transcriptome-wide association study (TWAS) was conducted to identify the genes whose imputed expressions were associated with AN and OCD, respectively. The mRNA expression profiles were analyzed by GEO2R to obtain differentially expressed genes. Gene set enrichment analysis was conducted to detect the spatial and temporal features related to AN and OCD using the TWAS and mRNA expression analysis results. We observed multiple common association signals shared by TWAS and mRNA expression analysis of AN, such as the primary auditory cortex vs. cerebellar cortex in fetal development and earlier vs. later fetal development in the somatosensory cortex. For OCD, we also detected multiple common association signals, such as medial prefrontal cortex vs. amygdala in adulthood and fetal development vs. infancy in mediodorsal nucleus of thalamus. Our study provides novel clues for describing the spatial and temporal features of brain development in the pathogenesis of AN and OCD.

摘要

我们的目的是探讨神经性厌食症 (AN) 和强迫症 (OCD) 的时空特征,考虑不同的脑区和发育阶段。从大脑时空转录组数据集获得与 16 个脑区和 9 个发育阶段相关的基因集。使用全基因组关联研究数据,进行转录组全基因组关联研究 (TWAS),以分别识别与 AN 和 OCD 相关的基因的表达情况。通过 GEO2R 分析 mRNA 表达谱,获得差异表达基因。使用 TWAS 和 mRNA 表达分析结果,进行基因集富集分析,以检测与 AN 和 OCD 相关的时空特征。我们观察到 TWAS 和 AN 的 mRNA 表达分析之间存在多个共同的关联信号,例如在胎儿发育过程中初级听觉皮层与小脑皮层相比,以及在躯体感觉皮层中早期与晚期胎儿发育相比。对于 OCD,我们还检测到多个共同的关联信号,例如在成年和胎儿发育与丘脑中背内侧核的婴儿期相比,内侧前额叶与杏仁核相比。我们的研究为描述 AN 和 OCD 发病机制中大脑发育的时空特征提供了新的线索。

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