颜林林 (2025-04-29 10:22):
#paper doi:10.1101/2025.04.27.25326490, medRxiv, 2025, GWAS of macro-scale resting state functional brain networks identify shared biology with brain structure and autism. 这篇文章对来自UK Biobank的54,030名个体的宏观静息态功能脑网络进行全基因组关联研究(GWAS),首先通过rs-fMRI构建功能脑网络,然后用图论方法总结出涵盖全球、半球和区域水平及其不对称性的多种指标,用这些指标结合SNP位点来做关联分析,找到七个显著的遗传位点和十个候选基因。此后,结合使用已发表的单细胞数据,把细胞类型特异表达与基因突变进行关联,并通过孟德尔随机化证明脑结构与神经表型的关系。然而,在针对12种神经疾病的分析中,仅发现孤独症与找到的图论指标存在显著关联。这篇文章综合了常见的各类方法,除了使用的人群规模较大外,并无特别创新之处,但作为方法运用案例进行学习还是不错的。
GWAS of macro-scale resting state functional brain networks identify shared biology with brain structure and autism
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Abstract:
The topology of the functional brain network has been associated with several neuropsychiatric conditions. However, little is known about its genetic underpinnings, and whether this overlaps with brain structure and neuropsychiatric conditions. Hence, we conducted genome-wide association study across six graph metrics of the macroscale functional networks at global, hemispheric and regional levels and their hemispheric asymmetry in 54,030 individuals. We identified seven experiment-wide significant loci and prioritised ten candidate genes. Both global graph metrics and hemispheric asymmetry are modestly heritable, but phenotypically and genetically form two clusters. Furthermore, cortical macro- and microstructure are causally related to global graph metrics and asymmetry, respectively, suggesting a dual structural constraint on functional network organisation. Finally, amongst twelve common neuropsychiatric conditions, only autism was genetically correlated with graph metrics of the functional network, supporting phenotypic case-control differences in functional connectivity. Overall, our results suggest different genetic axes shaping different aspects of brain functional topology and demonstrate shared biology with brain structure and autism.
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