دورية أكاديمية
Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts
| العنوان: | Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts |
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| المؤلفون: | Huckins, Laura M., Chatzinakos, Chris, Breen, Michael S., Hartmann, Jakob, Klengel, Torsten, da Silva Almeida, Ana C., Dobbyn, Amanda, Girdhar, Kiran, Hoffman, Gabriel E., Klengel, Claudia, Logue, Mark W., Lori, Adriana, Maihofer, Adam X., Morrison, Filomene G., Nguyen, Hoang T., Park, YongJin, Ruderfer, Douglas, Sloofman, Laura G., van Rooij, Sanne J.H., Baker, Dewleen G., Chen, Chia-Yen, Cox, Nancy, Duncan, Laramie E., Geyer, Mark A., Glatt, Stephen J., Im, Hae Kyung, Risbrough, Victoria B., Smoller, Jordan W., Stein, Dan J., Yehuda, Rachel, Liberzon, Israel, Koenen, Karestan C., Jovanovic, Tanja, Kellis, Manolis, Miller, Mark W., Bacanu, Silviu-Alin, Nievergelt, Caroline M., Buxbaum, Joseph D., Sklar, Pamela, Ressler, Kerry J., Stahl, Eli A., Daskalakis, Nikolaos P., PTSD Working Group of Psychiatric Genomics Consortium |
| المساهمون: | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| المصدر: | Elsevier |
| بيانات النشر: | Elsevier BV |
| سنة النشر: | 2021 |
| المجموعة: | DSpace@MIT (Massachusetts Institute of Technology) |
| الوصف: | To reveal post-traumatic stress disorder (PTSD) genetic risk influences on tissue-specific gene expression, we use brain and non-brain transcriptomic imputation. We impute genetically regulated gene expression (GReX) in 29,539 PTSD cases and 166,145 controls from 70 ancestry-specific cohorts and identify 18 significant GReX-PTSD associations corresponding to specific tissue-gene pairs. The results suggest substantial genetic heterogeneity based on ancestry, cohort type (military versus civilian), and sex. Two study-wide significant PTSD associations are identified in European and military European cohorts; ZNF140 is predicted to be upregulated in whole blood, and SNRNP35 is predicted to be downregulated in dorsolateral prefrontal cortex, respectively. In peripheral leukocytes from 175 marines, the observed PTSD differential gene expression correlates with the predicted differences for these individuals, and deployment stress produces glucocorticoid-regulated expression changes that include downregulation of both ZNF140 and SNRNP35. SNRNP35 knockdown in cells validates its functional role in U12-intron splicing. Finally, exogenous glucocorticoids in mice downregulate prefrontal Snrnp35 expression. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2211-1247 |
| العلاقة: | http://dx.doi.org/10.1016/j.celrep.2020.107716Test; Cell Reports; https://hdl.handle.net/1721.1/129399Test; Huckins, Laura M. et al. "Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts." Cell Reports 31, 9 (June 2020): 107716 © 2020 The Author(s) |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2020.107716Test https://hdl.handle.net/1721.1/129399Test |
| حقوق: | Creative Commons Attribution-NonCommercial-NoDerivs License ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.DF7A3CD1 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 22111247 |
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