Exome sequencing identifies novel genes associated with cerebellar volume and microstructure
Abstract Proteins encoded by exons are critical for cellular functions, and mutations in these genes often result in significant phenotypic effects. The cerebellum is linked to various heritable human disease phenotypes, yet genome-wide association studies have struggled to capture the effects of ra...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07797-3 |
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| author | Yuanyuan Liang Dongrui Ma Mengjie Li Zhiyun Wang Chenwei Hao Yuemeng Sun Xiaoyan Hao Chunyan Zuo Shuangjie Li Yanmei Feng Shasha Qi Yunpeng Wang Shilei Sun Yu-Ming Xu Ole A. Andreassen Changhe Shi |
| author_facet | Yuanyuan Liang Dongrui Ma Mengjie Li Zhiyun Wang Chenwei Hao Yuemeng Sun Xiaoyan Hao Chunyan Zuo Shuangjie Li Yanmei Feng Shasha Qi Yunpeng Wang Shilei Sun Yu-Ming Xu Ole A. Andreassen Changhe Shi |
| author_sort | Yuanyuan Liang |
| collection | DOAJ |
| description | Abstract Proteins encoded by exons are critical for cellular functions, and mutations in these genes often result in significant phenotypic effects. The cerebellum is linked to various heritable human disease phenotypes, yet genome-wide association studies have struggled to capture the effects of rare variants on cerebellar traits. This study conducts a large-scale exome association analysis using data from approximately 35,000 UK Biobank participants, examining seven cerebellar traits, including total cerebellar volume and white matter microstructure. We identify 90 genes associated with cerebellar traits, 60 of which were previously unreported in genome-wide association studies. Notable findings include the discovery of genes like PRKRA and TTK, as well as RASGRP3, linked to cerebellar volume and white matter microstructure. Gene enrichment analysis reveals associations with non-coding RNA processing, cognitive function, neurodegenerative diseases, and mental disorders, suggesting shared biological mechanisms between cerebellar phenotypes and neuropsychiatric diseases. |
| format | Article |
| id | doaj-art-b2d5d3ce89ea4e76b045c4fa3bae9387 |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-b2d5d3ce89ea4e76b045c4fa3bae93872025-08-20T03:03:40ZengNature PortfolioCommunications Biology2399-36422025-03-018111110.1038/s42003-025-07797-3Exome sequencing identifies novel genes associated with cerebellar volume and microstructureYuanyuan Liang0Dongrui Ma1Mengjie Li2Zhiyun Wang3Chenwei Hao4Yuemeng Sun5Xiaoyan Hao6Chunyan Zuo7Shuangjie Li8Yanmei Feng9Shasha Qi10Yunpeng Wang11Shilei Sun12Yu-Ming Xu13Ole A. Andreassen14Changhe Shi15Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityNORMENT, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of OsloDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityNORMENT, K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of OsloDepartment of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou UniversityAbstract Proteins encoded by exons are critical for cellular functions, and mutations in these genes often result in significant phenotypic effects. The cerebellum is linked to various heritable human disease phenotypes, yet genome-wide association studies have struggled to capture the effects of rare variants on cerebellar traits. This study conducts a large-scale exome association analysis using data from approximately 35,000 UK Biobank participants, examining seven cerebellar traits, including total cerebellar volume and white matter microstructure. We identify 90 genes associated with cerebellar traits, 60 of which were previously unreported in genome-wide association studies. Notable findings include the discovery of genes like PRKRA and TTK, as well as RASGRP3, linked to cerebellar volume and white matter microstructure. Gene enrichment analysis reveals associations with non-coding RNA processing, cognitive function, neurodegenerative diseases, and mental disorders, suggesting shared biological mechanisms between cerebellar phenotypes and neuropsychiatric diseases.https://doi.org/10.1038/s42003-025-07797-3 |
| spellingShingle | Yuanyuan Liang Dongrui Ma Mengjie Li Zhiyun Wang Chenwei Hao Yuemeng Sun Xiaoyan Hao Chunyan Zuo Shuangjie Li Yanmei Feng Shasha Qi Yunpeng Wang Shilei Sun Yu-Ming Xu Ole A. Andreassen Changhe Shi Exome sequencing identifies novel genes associated with cerebellar volume and microstructure Communications Biology |
| title | Exome sequencing identifies novel genes associated with cerebellar volume and microstructure |
| title_full | Exome sequencing identifies novel genes associated with cerebellar volume and microstructure |
| title_fullStr | Exome sequencing identifies novel genes associated with cerebellar volume and microstructure |
| title_full_unstemmed | Exome sequencing identifies novel genes associated with cerebellar volume and microstructure |
| title_short | Exome sequencing identifies novel genes associated with cerebellar volume and microstructure |
| title_sort | exome sequencing identifies novel genes associated with cerebellar volume and microstructure |
| url | https://doi.org/10.1038/s42003-025-07797-3 |
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