Genome-wide association study unravels mechanisms of brain glymphatic activity
Abstract 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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55706-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594549595176960 |
|---|---|
| author | 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 IMAGEN Consortium Jian-Feng Feng Ya-Ru Zhang Wei Cheng Jin-Tai Yu |
| author_facet | 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 IMAGEN Consortium Jian-Feng Feng Ya-Ru Zhang Wei Cheng Jin-Tai Yu |
| author_sort | Shu-Yi Huang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-6345398ee3b04ce2bd72341693f49712 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-6345398ee3b04ce2bd72341693f497122025-01-19T12:30:32ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-55706-9Genome-wide association study unravels mechanisms of brain glymphatic activityShu-Yi Huang0Yi-Jun Ge1Peng Ren2Bang-Sheng Wu3Weikang Gong4Jing Du5Shi-Dong Chen6Ju-Jiao Kang7Qing Ma8Arun L. W. Bokde9Sylvane Desrivières10Hugh Garavan11Antoine Grigis12Herve Lemaitre13Michael N. Smolka14Sarah Hohmann15IMAGEN ConsortiumJian-Feng Feng16Ya-Ru Zhang17Wei Cheng18Jin-Tai Yu19Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversitySchool of Data Science, Fudan UniversityCentre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, UNSWDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityDiscipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College DublinSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s CollegeDepartments of Psychiatry and Psychology, University of VermontNeuroSpin, CEA, Université Paris-SaclayNeuroSpin, CEA, Université Paris-SaclayDepartment of Psychiatry and Psychotherapy, Technische Universität DresdenDepartment of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityAbstract 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.https://doi.org/10.1038/s41467-024-55706-9 |
| spellingShingle | 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 IMAGEN Consortium Jian-Feng Feng Ya-Ru Zhang Wei Cheng Jin-Tai Yu Genome-wide association study unravels mechanisms of brain glymphatic activity Nature Communications |
| title | Genome-wide association study unravels mechanisms of brain glymphatic activity |
| title_full | Genome-wide association study unravels mechanisms of brain glymphatic activity |
| title_fullStr | Genome-wide association study unravels mechanisms of brain glymphatic activity |
| title_full_unstemmed | Genome-wide association study unravels mechanisms of brain glymphatic activity |
| title_short | Genome-wide association study unravels mechanisms of brain glymphatic activity |
| title_sort | genome wide association study unravels mechanisms of brain glymphatic activity |
| url | https://doi.org/10.1038/s41467-024-55706-9 |
| work_keys_str_mv | AT shuyihuang genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT yijunge genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT pengren genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT bangshengwu genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT weikanggong genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT jingdu genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT shidongchen genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT jujiaokang genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT qingma genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT arunlwbokde genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT sylvanedesrivieres genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT hughgaravan genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT antoinegrigis genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT hervelemaitre genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT michaelnsmolka genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT sarahhohmann genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT imagenconsortium genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT jianfengfeng genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT yaruzhang genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT weicheng genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity AT jintaiyu genomewideassociationstudyunravelsmechanismsofbrainglymphaticactivity |