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Novel Genes Associated With Working Memory Are Identified by Combining Connectome Transcriptome and Genome

机译:通过结合连接组、转录组和基因组来识别与工作记忆相关的新基因

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摘要

Working memory (WM) plays a crucial role in human cognition. Previous candidate and genome‐wide association studies have reported many genetic variations associated with WM. However, little research has examined genetic basis of WM by using transcriptome, even though it reflects gene function more directly than does the genome. Here we propose a new approach to exploring the genetic mechanisms of WM by integrating connectome, transcriptome, and genome data in a high‐quality dataset comprising 481 Chinese healthy adults. First, relevance vector regression was used to define WM‐related brain regions. Second, genes differentially expressed within these regions were identified using the Allen Human Brain Atlas (AHBA) dataset. Finally, two independent datasets were used to validate these genes' contributions to WM. With this method, we identified 24 novel genes and 20 of them were confirmed in the large‐scale datasets of ABCD and UK Biobank. These novel genes were enriched in the cellular component of collagen‐containing extracellular matrix and the CCL18 signaling pathway. Our method offers an effective approach to integrating multimodal gene discovery and demonstrates the superiority of expression data. This new method and the newly identified genes deserve more attention in the future.
机译:工作记忆 (WM) 在人类认知中起着至关重要的作用。以前的候选和全基因组关联研究报道了许多与 WM 相关的遗传变异。然而,很少有研究通过使用转录组来检查 WM 的遗传基础,尽管它比基因组更直接地反映了基因功能。在这里,我们提出了一种探索 WM 遗传机制的新方法,通过将连接组、转录组和基因组数据整合到一个包含 481 名中国健康成年人的高质量数据集中。首先,使用相关性向量回归来定义与 WM 相关的大脑区域。其次,使用 Allen Human Brain Atlas (AHBA) 数据集鉴定在这些区域内差异表达的基因。最后,使用两个独立的数据集来验证这些基因对 WM 的贡献。通过这种方法,我们鉴定了 24 个新基因,其中 20 个在 ABCD 和 UK Biobank 的大规模数据集中得到证实。这些新基因富集在含胶原蛋白的细胞外基质的细胞成分和 CCL18 信号通路中。我们的方法提供了一种整合多模式基因发现的有效方法,并证明了表达数据的优越性。这种新方法和新发现的基因在未来值得更多关注。

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