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通过双聚类在多个性状中鉴定出共享的多基因风险评分和体素级灰质相关集。

Shared sets of correlated polygenic risk scores and voxel-wise grey matter across multiple traits identified via bi-clustering.

出版信息

Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:2201-2206. doi: 10.1109/EMBC46164.2021.9630825.

DOI:10.1109/EMBC46164.2021.9630825
PMID:34891724
Abstract

Neuropsychiatric disorders involve complex polygenic determinants as well as brain alterations. The combination of genetic inheritance and neuroimaging approaches could advance our understanding of psychiatric disorders. However, cross-disorder overlap is a current issue since psychiatric conditions share some neurogenetic correlates, symptoms, and brain effects. Exploring the impact of genetic risk on the brain across disorders could help understand commonalities across multiple psychopathologies. To do this, we first compute the linear relationship between PRS and voxel-wise grey matter volume to generate brain maps for five psychiatric and three control traits. Next, we use the biclustering approach to identify regions of the brain associated with polygenic risk scores in one or more traits. Our results demonstrate a significant overlap in brain regions connected to polygenic risk across psychiatric traits. Moreover, such brain domains are highly allied with the polygenic risk for non-psychiatric control traits. This multi-trait overlap characterizes the nonspecific relationship between neural anatomy and inherited risk factors in psychiatric conditions, and in some cases, the overlap in neural features linked to genetic risk for non-psychiatric attributes.Clinical Relevance-This study presents biclusters of multiple psychiatric and control traits. The analysis reported various brain regions, including cerebellum, cuneus, precuneus, fusiform, supplementary motor area, that show significant correlation with polygenic risk scores across diverse groups of psychiatric conditions and non-psychiatric control traits.

摘要

神经精神疾病涉及复杂的多基因决定因素以及大脑改变。遗传继承和神经影像学方法的结合可以增进我们对精神疾病的理解。然而,跨疾病重叠是一个当前的问题,因为精神疾病具有一些神经遗传相关性、症状和大脑效应。探索遗传风险对跨疾病大脑的影响可以帮助理解多种精神病理学的共性。为此,我们首先计算 PRS 和体素灰质体积之间的线性关系,以生成五个精神疾病和三个对照特征的大脑图谱。接下来,我们使用双聚类方法来识别与一个或多个特征中的多基因风险评分相关的大脑区域。我们的结果表明,跨精神疾病特征的多基因风险相关的大脑区域存在显著重叠。此外,这些大脑区域与非精神疾病对照特征的多基因风险高度相关。这种多特征重叠特征描述了神经解剖结构与精神疾病中遗传风险因素之间的非特异性关系,在某些情况下,与非精神疾病属性的遗传风险相关的神经特征也存在重叠。

临床意义-本研究呈现了多个精神疾病和对照特征的双聚类。该分析报告了各种大脑区域,包括小脑、楔前叶、楔叶、梭状回、补充运动区,它们与跨多种精神疾病组和非精神疾病对照特征的多基因风险评分显著相关。

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