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Genome-wide association study unravels mechanisms of brain glymphatic activity

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significa...

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Main Authors: Huang, Shu-Yi (Author) , Ge, Yi-Jun (Author) , Ren, Peng (Author) , Wu, Bang-Sheng (Author) , Gong, Weikang (Author) , Du, Jing (Author) , Chen, Shi-Dong (Author) , Kang, Ju-Jiao (Author) , Ma, Qing (Author) , Bokde, Arun L. W. (Author) , Desrivières, Sylvane (Author) , Garavan, Hugh (Author) , Grigis, Antoine (Author) , Lemaître, Hervé (Author) , Smolka, Michael (Author) , Hohmann, Sarah (Author) , Feng, Jian-Feng (Author) , Zhang, Ya-Ru (Author) , Cheng, Wei (Author) , Yu, Jin-Tai (Author)
Format: Article (Journal)
Language:English
Published: 13 January 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-17
ISSN:2041-1723
DOI:10.1038/s41467-024-55706-9
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-024-55706-9
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-024-55706-9
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Author Notes:Shu-Yi Huang, Yi-Jun Ge, Peng Ren, Bang-Sheng Wu, Weikang Gong, Jing Du, Shi-Dong Chen, Ju-Jiao Kang, Qing Ma, Arun L. W. Bokde, Sylvane Desrivières, Hugh Garavan, Antoine Grigis, Herve Lemaitre, Michael N. Smolka, Sarah Hohmann, Jian-Feng Feng, Ya-Ru Zhang, Wei Cheng, and Jin-Tai Yu
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Summary:Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets. Genetic signals located at the 2p23.3 locus yielded significantly concordant effects in both young and aging cohorts. Genetic correlation and polygenic overlap analyses indicate a common underlying genetic mechanism between the ALPS-index, ventricular volumes, and cerebrospinal fluid tau levels, with GMNC (3q28) and C16orf95 (16q24.2) as the shared genetic basis. Our findings enhance the understanding of the genetics of the ALPS-index and provide insight for further research into the neurobiological mechanisms of glymphatic clearance activity across the lifespan and its relation to neuropsychiatric phenotypes.
Item Description:Gesehen am 23.07.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-55706-9

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