General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.
General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.
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皮质基因表达的一般和特定模式作为复杂认知功能的空间关联。
DOI：
10.1101/2023.03.16.532915
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Stolic
中科院分区：
文献类型：
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作者：
Moodie,JoannaE;Harris,SarahE;Harris,MathewA;Buchanan,ColinR;Davies,Gail;Taylor,Adele;Redmond,Paul;Liewald,David;DelCValdésHernández,Maria;Shenkin,Susan;Russ,TomC;MuñozManiega,Susana;Luciano,Michelle;Corley,Janie;Stolic
大脑中的基因表达各不相同。这种空间模式表示对特定大脑功能的专门支持。然而，特定基因的表达在大脑中波动的方式可能受到一般规则的控制。量化跨基因的空间共变模式将有助于深入了解支持复杂认知功能等大脑区域的分子特征。在这里，我们使用主成分分析来区分一般和独特的基因调控与认知皮质基质的关联。我们发现 8235 个基因的皮质表达谱的区域间变异在两个主要主要成分中存在共变：基因本体分析表明这些维度的特征是细胞信号传导/修饰和转录因子的下调和上调。我们在样本外和不同的数据处理选择中验证这些模式。与一般认知功能密切相关的大脑区域（g；3个队列，总荟萃分析N= 39,519）往往在两个主要成分的下调和上调之间更加平衡（由区域成分分数表示）。然后，我们进一步确定了 29 个基因作为 g 的候选皮质空间相关基因，超出了两个主要成分的模式（|β|范围 = 0.18 至 0.53）。其中许多基因先前已与临床神经退行性和精神疾病或其他健康相关表型相关。这些结果提供了对基因表达的皮质组织及其与认知功能个体差异的关联的见解。
Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regulatory associations with cortical substrates of cognition. We find that the region‐to‐region variation in cortical expression profiles of 8235 genes covaries across two major principal components: gene ontology analysis suggests these dimensions are characterised by downregulation and upregulation of cell‐signalling/modification and transcription factors. We validate these patterns out‐of‐sample and across different data processing choices. Brain regions more strongly implicated in general cognitive functioning (g; 3 cohorts, total meta‐analyticN= 39,519) tend to be more balanced between downregulation and upregulation of both major components (indicated by regional component scores). We then identify a further 29 genes as candidate cortical spatial correlates ofg, beyond the patterning of the two major components (|β| range = 0.18 to 0.53). Many of these genes have been previously associated with clinical neurodegenerative and psychiatric disorders, or with other health‐related phenotypes. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning.