دورية أكاديمية
Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia
| العنوان: | Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia |
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| المؤلفون: | Palmer, D. S., Howrigan, D. P., Chapman, S. B., Adolfsson, R., Bass, N., Blackwood, D., Boks, M. P. M., Chen, C., Churchhouse, C., Corvin, A. P., Craddock, N., Curtis, D., Di Florio, A., Dickerson, F., Freimer, N. B., Goes, F. S., Jia, X., Jones, I., Jones, Lisa, Jonsson, L., Kahn, R. S., Landén, M., Locke, A. E., McIntosh, A. M., McQuillin, A., Morris, D. W., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pedersen, N. L., Posthuma, D., Reif, A., Risch, N., Schaefer, C., Scott, L., Singh, T., Smoller, J. W., Solomonson, M., St Clair, D., Stahl, E. A., Vreeker, A., Walters, J. T. R., Wang, W., Watts, N. A., Yolken, R., Zandi, P. P., Neale, B. M. |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2022 |
| المجموعة: | University of Worcester: Worcester Research and Publications |
| مصطلحات موضوعية: | BF Psychology, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
| الوصف: | We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD’s polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://eprints.worc.ac.uk/11537/1/Exome%20sequencing%20in%20bipolar%20disorder%20reveals%20AKAP11%20as%20a%20risk%20gene%20shared%20with%20schizophrenia.docxTest; https://eprints.worc.ac.uk/11537/3/Exome%20sequencing%20in%20bipolar%20disorder%20reveals%20AKAP11%20as%20a%20risk%20gene%20shared%20with%20schizophrenia.pdfTest; Palmer, D. S., Howrigan, D. P., Chapman, S. B., Adolfsson, R., Bass, N., Blackwood, D., Boks, M. P. M., Chen, C., Churchhouse, C., Corvin, A. P., Craddock, N., Curtis, D., Di Florio, A., Dickerson, F., Freimer, N. B., Goes, F. S., Jia, X., Jones, I., Jones, Lisa orcid:0000-0002-5122-8334 , Jonsson, L., Kahn, R. S., Landén, M., Locke, A. E., McIntosh, A. M., McQuillin, A., Morris, D. W., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pedersen, N. L., Posthuma, D., Reif, A., Risch, N., Schaefer, C., Scott, L., Singh, T., Smoller, J. W., Solomonson, M., St Clair, D., Stahl, E. A., Vreeker, A., Walters, J. T. R., Wang, W., Watts, N. A., Yolken, R., Zandi, P. P. and Neale, B. M. (2022) Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia. Nature Genetics, 54. pp. 541-547. ISSN 1546-1718 (online) 1061-4036 (print) |
| DOI: | 10.1038/s41588-022-01034-x |
| الإتاحة: | https://doi.org/10.1038/s41588-022-01034-xTest http://eprints.worc.ac.uk/11537Test/ https://eprints.worc.ac.uk/11537/1/Exome%20sequencing%20in%20bipolar%20disorder%20reveals%20AKAP11%20as%20a%20risk%20gene%20shared%20with%20schizophrenia.docxTest https://eprints.worc.ac.uk/11537/3/Exome%20sequencing%20in%20bipolar%20disorder%20reveals%20AKAP11%20as%20a%20risk%20gene%20shared%20with%20schizophrenia.pdfTest |
| رقم الانضمام: | edsbas.FDD04BCE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41588-022-01034-x |
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