Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts
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1-s2.0-S2211124720306938-main.pdf
Description
Published version
Size
2.56 MB
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Checksum (MD5)
b174f47b04088a7754847bab35698cea
Author(s)
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
Date Issued
June 2020
Journal
Cell Reports
Publisher
Elsevier BV
Citation
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)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2020.107716
