Donate

Publication

Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts

Citation:
Cell Reports. 2020; Jun 2;31(9):107716. doi: 10.1016/j.celrep.2020.107716.
Authored By:
Huckins LM, Chatzinakos C, Breen MS, Hartmann J, Klengel T, da Silva Almeida AC, Dobbyn A, Girdhar K, Hoffman GE, Klengel C, Logue MW, Lori A, Maihofer AX, Morrison FG, Nguyen HT, Park Y, Ruderfer D, Sloofman LG, van Rooij SJH; PTSD Working Group of Psychiatric Genomics Consortium, Baker DG, Chen CY, Cox N, Duncan LE, Geyer MA, Glatt SJ, Im HK, Risbrough VB, Smoller JW, Stein DJ, Yehuda R, Liberzon I, Koenen KC, Jovanovic T, Kellis M, Miller MW, Bacanu SA, Nievergelt CM, Buxbaum JD, Sklar P, Ressler KJ, Stahl EA, Daskalakis NP.
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.
Published in:
Cell Reports
View article

More Publications

August 1, 2023

Journal of Psychopharmacology

Improving Translational Relevance in Preclinical Psychopharmacology (iTRIPP)

View
July 6, 2023

Gerontology and Geriatric Medicine

Caring for Dementia Caregivers: Understanding Caregiver Stress During the COVID-19 Pandemic

View
May 19, 2023

Nature Reviews Neurology

Global synergistic actions to improve brain health for human development

View
April 20, 2023

Nature Mental Health

Machine learning-based identification of a psychotherapy-predictive electroencephalographic signature in PTSD

View
February 21, 2023

Translational Psychiatry

Screening for PTSD and TBI in Veterans using Routine Clinical Laboratory Blood Tests

View
February 13, 2023

Frontiers in Aging Neuroscience

Machine learning within the Parkinson’s progression markers initiative: Review of the current state of affairs

View
View All

Cohen Veterans Bioscience is a non-profit 501(c)(3) biomedical research and technology organization dedicated to advancing brain health by fast-tracking precision diagnostics and tailored therapeutics.

Cohen Veterans Bioscience is a non-profit 501(c)(3) biomedical research and technology organization dedicated to advancing brain health by fast-tracking precision diagnostics and tailored therapeutics.

©2023 Cohen Veterans Bioscience |  Privacy Policy | Terms of Use

Newsletter
Donate