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与出生时白质改变相关的自闭症常见变异:来自人类发育连接组计划的221名欧洲足月儿的基于固定点的横断面分析

Autism common variants associated with white matter alterations at birth: cross-sectional fixel-based analyses of 221 European term-born neonates from the developing human connectome project.

作者信息

Le Hai, Bonthrone Alexandra F, Uus Alena, Fenchel Daphna, Lautarescu Alexandra, Dimitrakopoulou Konstantina, Edwards A David, Hajnal Joseph V, Counsell Serena J, Cordero-Grande Lucilio, Christiaens Daan, Batalle Dafnis, Pietsch Maximilian, Price Anthony N, Patel Hamel, Curtis Charles, Cullen Harriet, Deprez Maria, Tournier Jacques-Donald

机构信息

Research Department of Early Life Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

出版信息

Transl Psychiatry. 2025 Feb 4;15(1):40. doi: 10.1038/s41398-025-03252-3.

Abstract

Increasing lines of evidence suggest white matter (WM) structural changes associated with autism can be detected in the first year of life. Despite the condition having high heritability, the relationship between autism common genetic variants and WM changes during this period remains unclear. By employing advanced regional and whole-brain fixel-based analysis, the current study investigated the association between autism polygenic scores (PS) and WM microscopic fibre density and macrostructural morphology in 221 term-born infants of European ancestry from the developing Human Connectome Project. The results suggest greater tract mean fibre-bundle cross-section of the left superior corona radiata is associated with higher autism PS. Subsequent exploratory enrichment analysis revealed that the autism risk single nucleotide polymorphisms most associated with the imaging phenotype may have roles in neuronal cellular components. Together, these findings suggest a possible link between autism common variants and early WM development.

摘要

越来越多的证据表明,与自闭症相关的白质(WM)结构变化在生命的第一年就可以被检测到。尽管这种疾病具有高度遗传性,但在此期间自闭症常见基因变异与WM变化之间的关系仍不清楚。通过采用先进的基于体素的区域和全脑分析,本研究调查了来自正在进行的人类连接组计划的221名欧洲血统足月出生婴儿的自闭症多基因评分(PS)与WM微观纤维密度和宏观结构形态之间的关联。结果表明,左额上回放射冠束平均纤维束横截面积越大,自闭症PS越高。随后的探索性富集分析表明,与成像表型最相关的自闭症风险单核苷酸多态性可能在神经元细胞成分中起作用。总之,这些发现表明自闭症常见变异与早期WM发育之间可能存在联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5326/11794609/83bd9354cd7f/41398_2025_3252_Fig1_HTML.jpg

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