Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders
Abstract Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic and transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) and weighted gene co-expression network analysis (WGCNA) to explore shared mechanism between psychiatri...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07481-6 |
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| author | Huanxin Ding Yue Jiang Qing Sun Yingchao Song Shuohui Dong Qian Xu Linzehao Li Chuxuan Liu Bingjun Li Hengxuan Jiang Bichen Peng Shi Peng Chumeng Zhang Jiankang Zhu Mingwei Zhong Guangyong Zhang Xiao Chang |
| author_facet | Huanxin Ding Yue Jiang Qing Sun Yingchao Song Shuohui Dong Qian Xu Linzehao Li Chuxuan Liu Bingjun Li Hengxuan Jiang Bichen Peng Shi Peng Chumeng Zhang Jiankang Zhu Mingwei Zhong Guangyong Zhang Xiao Chang |
| author_sort | Huanxin Ding |
| collection | DOAJ |
| description | Abstract Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic and transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) and weighted gene co-expression network analysis (WGCNA) to explore shared mechanism between psychiatric and gastrointestinal disorders. Significant genetic correlations were found between these disorders, especially in irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), depression (DEP), and neuroticism (NE). MTAG identify 60 novel pleiotropic loci for IBS and 14 for GERD, predominantly located near genes associated with neurological pathways. Further WGCNA identifies multiple co-expression modules enriched with genes involved in neurological pathways in digestive tissues, with some modules strongly preserved across brain and digestive tissues. Moreover, our network analysis suggests BSN, CELF4, and NRXN1 as central players in the regulation of the gut-brain axis (GBA). This study enhances our understanding of the GBA and underscores BSN, CELF4, and NRXN1 as crucial targets for future research. |
| format | Article |
| id | doaj-art-2cc0c703b6574ed68243c149a4b66b62 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-2cc0c703b6574ed68243c149a4b66b622025-01-19T12:35:22ZengNature PortfolioCommunications Biology2399-36422025-01-018111410.1038/s42003-025-07481-6Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disordersHuanxin Ding0Yue Jiang1Qing Sun2Yingchao Song3Shuohui Dong4Qian Xu5Linzehao Li6Chuxuan Liu7Bingjun Li8Hengxuan Jiang9Bichen Peng10Shi Peng11Chumeng Zhang12Jiankang Zhu13Mingwei Zhong14Guangyong Zhang15Xiao Chang16Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalCollege of Medical Information and Artificial Intelligence, Shandong First Medical University & Shandong Academy of Medical SciencesDepartment of Gastroentero-Anorectal Surgery, Zhuji People’s Hospital of Zhejiang ProvinceCollege of Medical Information and Artificial Intelligence, Shandong First Medical University & Shandong Academy of Medical SciencesDepartment of General Surgery, Qilu Hospital of Shandong UniversityDepartment of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalCollege of Medical Information and Artificial Intelligence, Shandong First Medical University & Shandong Academy of Medical SciencesDepartment of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalDepartment of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalCollege of Medical Information and Artificial Intelligence, Shandong First Medical University & Shandong Academy of Medical SciencesCollege of Medical Information and Artificial Intelligence, Shandong First Medical University & Shandong Academy of Medical SciencesDepartment of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalCollege of Medical Information and Artificial Intelligence, Shandong First Medical University & Shandong Academy of Medical SciencesDepartment of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalDepartment of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalDepartment of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalCollege of Medical Information and Artificial Intelligence, Shandong First Medical University & Shandong Academy of Medical SciencesAbstract Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic and transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) and weighted gene co-expression network analysis (WGCNA) to explore shared mechanism between psychiatric and gastrointestinal disorders. Significant genetic correlations were found between these disorders, especially in irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), depression (DEP), and neuroticism (NE). MTAG identify 60 novel pleiotropic loci for IBS and 14 for GERD, predominantly located near genes associated with neurological pathways. Further WGCNA identifies multiple co-expression modules enriched with genes involved in neurological pathways in digestive tissues, with some modules strongly preserved across brain and digestive tissues. Moreover, our network analysis suggests BSN, CELF4, and NRXN1 as central players in the regulation of the gut-brain axis (GBA). This study enhances our understanding of the GBA and underscores BSN, CELF4, and NRXN1 as crucial targets for future research.https://doi.org/10.1038/s42003-025-07481-6 |
| spellingShingle | Huanxin Ding Yue Jiang Qing Sun Yingchao Song Shuohui Dong Qian Xu Linzehao Li Chuxuan Liu Bingjun Li Hengxuan Jiang Bichen Peng Shi Peng Chumeng Zhang Jiankang Zhu Mingwei Zhong Guangyong Zhang Xiao Chang Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders Communications Biology |
| title | Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders |
| title_full | Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders |
| title_fullStr | Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders |
| title_full_unstemmed | Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders |
| title_short | Integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders |
| title_sort | integrating genetics and transcriptomics to characterize shared mechanisms in digestive diseases and psychiatric disorders |
| url | https://doi.org/10.1038/s42003-025-07481-6 |
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