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Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts.
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.
Afiliação
  • Huckins LM; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 1002
  • Chatzinakos C; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Breen MS; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10
  • Hartmann J; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
  • Klengel T; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen 37075, Germany.
  • da Silva Almeida AC; Department of Biotherapeutic and Medicinal Sciences, Biogen, Cambridge, MA, 02142, USA.
  • Dobbyn A; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 1002
  • Girdhar K; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 1002
  • Hoffman GE; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 1002
  • Klengel C; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
  • Logue MW; National Center for PTSD at VA Boston Healthcare System, Boston, MA 02130, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA; Biomedical Genetics, Boston University School of Medicine, Boston, MA 02118, USA; Department of Biostatistics, Boston University Scho
  • Lori A; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA.
  • Maihofer AX; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Excellence in Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA; Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
  • Morrison FG; National Center for PTSD at VA Boston Healthcare System, Boston, MA 02130, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA.
  • Nguyen HT; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 1002
  • Park Y; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ruderfer D; Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Sloofman LG; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 1002
  • van Rooij SJH; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA.
  • Baker DG; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Excellence in Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA; Psychiatry Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, US
  • Chen CY; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Psychiatric & Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Analytic an
  • Cox N; Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Duncan LE; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
  • Geyer MA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Excellence in Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA; Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
  • Glatt SJ; Department of Psychiatry and Behavioral Sciences, State University of New York - Upstate Medical University, Syracuse, NY, 13210, USA.
  • Im HK; Department of Medicine, Section of Genetic Medicine, The University of Chicago, Chicago, IL 60637, USA; Center for Translational Data Science, The University of Chicago, Chicago, IL 60616, USA.
  • Risbrough VB; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Excellence in Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA; Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
  • Smoller JW; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Psychiatric & Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Analytic an
  • Stein DJ; SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town 7700, South Africa.
  • Yehuda R; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mental Health Care Center, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY 10468, USA.
  • Liberzon I; Department of Psychiatry and Behavioral Science, Texas A&M University College of Medicine, Bryan, TX 77807, USA.
  • Koenen KC; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Psychiatric & Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department
  • Jovanovic T; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA; Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, MI, USA.
  • Kellis M; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Miller MW; National Center for PTSD at VA Boston Healthcare System, Boston, MA 02130, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA.
  • Bacanu SA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Nievergelt CM; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Excellence in Stress and Mental Health, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA; Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
  • Buxbaum JD; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, N
  • Sklar P; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 1002
  • Ressler KJ; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
  • Stahl EA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 1002
  • Daskalakis NP; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic add
Cell Rep ; 31(9): 107716, 2020 06 02.
Article em En | MEDLINE | ID: mdl-32492425
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtornos de Estresse Pós-Traumáticos / Ribonucleoproteínas Nucleares Pequenas / Córtex Pré-Frontal Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtornos de Estresse Pós-Traumáticos / Ribonucleoproteínas Nucleares Pequenas / Córtex Pré-Frontal Tipo de estudo: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article