Shared genetic links between frontotemporal dementia and psychiatric disorders
Abstract Background Epidemiological and clinical studies have suggested comorbidity between frontotemporal dementia (FTD) and psychiatric disorders. FTD patients carrying specific mutations were at higher risk for some psychiatric disorders, and vice versa, implying potential shared genetic etiology...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12916-022-02335-y |
| _version_ | 1818195698298912768 |
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| author | Chunyu Li Dejiang Pang Junyu Lin Tianmi Yang Huifang Shang |
| author_facet | Chunyu Li Dejiang Pang Junyu Lin Tianmi Yang Huifang Shang |
| author_sort | Chunyu Li |
| collection | DOAJ |
| description | Abstract Background Epidemiological and clinical studies have suggested comorbidity between frontotemporal dementia (FTD) and psychiatric disorders. FTD patients carrying specific mutations were at higher risk for some psychiatric disorders, and vice versa, implying potential shared genetic etiology, which is still less explored. Methods We examined the genetic correlation using summary statistics from genome-wide association studies and analyzed their genetic enrichment leveraging the conditional false discovery rate method. Furthermore, we explored the causal association between FTD and psychiatric disorders with Mendelian randomization (MR) analysis. Results We identified a significant genetic correlation between FTD and schizophrenia at both genetic and transcriptomic levels. Meanwhile, robust genetic enrichment was observed between FTD and schizophrenia and alcohol use disorder. Seven shared genetic loci were identified, which were mainly involved in interleukin-induced signaling, synaptic vesicle, and brain-derived neurotrophic factor signaling pathways. By integrating cis-expression quantitative trait loci analysis, we identified MAPT and CADM2 as shared risk genes. MR analysis showed mutual causation between FTD and schizophrenia with nominal association. Conclusions Our findings provide evidence of shared etiology between FTD and schizophrenia and indicate potential common molecular mechanisms contributing to the overlapping pathophysiological and clinical characteristics. Our results also demonstrate the essential role of autoimmunity in these diseases. These findings provide a better understanding of the pleiotropy between FTD and psychiatric disorders and have implications for therapeutic trials. Graphical abstract |
| first_indexed | 2024-12-12T01:22:19Z |
| format | Article |
| id | doaj.art-bf157f865dad44e993e51bd5d92e0b24 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-12-12T01:22:19Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-bf157f865dad44e993e51bd5d92e0b242022-12-22T00:43:12ZengBMCBMC Medicine1741-70152022-05-0120111310.1186/s12916-022-02335-yShared genetic links between frontotemporal dementia and psychiatric disordersChunyu Li0Dejiang Pang1Junyu Lin2Tianmi Yang3Huifang Shang4Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatric, West China Hospital, Sichuan UniversityDepartment of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatric, West China Hospital, Sichuan UniversityDepartment of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatric, West China Hospital, Sichuan UniversityDepartment of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatric, West China Hospital, Sichuan UniversityDepartment of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatric, West China Hospital, Sichuan UniversityAbstract Background Epidemiological and clinical studies have suggested comorbidity between frontotemporal dementia (FTD) and psychiatric disorders. FTD patients carrying specific mutations were at higher risk for some psychiatric disorders, and vice versa, implying potential shared genetic etiology, which is still less explored. Methods We examined the genetic correlation using summary statistics from genome-wide association studies and analyzed their genetic enrichment leveraging the conditional false discovery rate method. Furthermore, we explored the causal association between FTD and psychiatric disorders with Mendelian randomization (MR) analysis. Results We identified a significant genetic correlation between FTD and schizophrenia at both genetic and transcriptomic levels. Meanwhile, robust genetic enrichment was observed between FTD and schizophrenia and alcohol use disorder. Seven shared genetic loci were identified, which were mainly involved in interleukin-induced signaling, synaptic vesicle, and brain-derived neurotrophic factor signaling pathways. By integrating cis-expression quantitative trait loci analysis, we identified MAPT and CADM2 as shared risk genes. MR analysis showed mutual causation between FTD and schizophrenia with nominal association. Conclusions Our findings provide evidence of shared etiology between FTD and schizophrenia and indicate potential common molecular mechanisms contributing to the overlapping pathophysiological and clinical characteristics. Our results also demonstrate the essential role of autoimmunity in these diseases. These findings provide a better understanding of the pleiotropy between FTD and psychiatric disorders and have implications for therapeutic trials. Graphical abstracthttps://doi.org/10.1186/s12916-022-02335-yFrontotemporal dementiaPsychiatric disordersGenetic correlationMendelian randomization |
| spellingShingle | Chunyu Li Dejiang Pang Junyu Lin Tianmi Yang Huifang Shang Shared genetic links between frontotemporal dementia and psychiatric disorders BMC Medicine Frontotemporal dementia Psychiatric disorders Genetic correlation Mendelian randomization |
| title | Shared genetic links between frontotemporal dementia and psychiatric disorders |
| title_full | Shared genetic links between frontotemporal dementia and psychiatric disorders |
| title_fullStr | Shared genetic links between frontotemporal dementia and psychiatric disorders |
| title_full_unstemmed | Shared genetic links between frontotemporal dementia and psychiatric disorders |
| title_short | Shared genetic links between frontotemporal dementia and psychiatric disorders |
| title_sort | shared genetic links between frontotemporal dementia and psychiatric disorders |
| topic | Frontotemporal dementia Psychiatric disorders Genetic correlation Mendelian randomization |
| url | https://doi.org/10.1186/s12916-022-02335-y |
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