puc-header

Analysis of Genetically Regulated Gene Expression Identifies a Trauma Type Specific PTSD Gene, SNRNP35

53 Pages Posted: 19 Mar 2019 Publication Status: Review Complete

See all articles by Laura M. Huckins

Laura M. Huckins

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

Michael S Breen

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Mount Sinai Health System - Seaver Autism Center for Research and Treatment; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

Chris Chatzinakos

Virginia Commonwealth University (VCU) - Department of Psychiatry

Jakob Hartmann

Harvard University - Department of Psychiatry

Torsten Klengel

Harvard University - Department of Psychiatry; University Medical Center Goettingen - Department of Psychiatry and Psychotherapy

Ana C da Silva Almeida

Biogen - Department of Biotherapeutic and Medicinal Sciences

Amanda Dobbyn

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

Kiran Girdhar

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

Gabriel E Hoffman

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology; Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics

Claudia Klengel

Harvard University - Department of Psychiatry

Mark W Logue

National Center for PTSD at VA Boston Healthcare; Boston University - Department of Psychiatry; Boston University - Biomedical Genetics; Boston University - Department of Biostatistics

Adriana Lori

Emory University - Department of Psychiatry and Behavioral Sciences

Filomene G Morrison

National Center for PTSD at VA Boston Healthcare; Boston University - Department of Psychiatry

Hoang T Nguyen

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

Yongjin Park

Massachusetts Institute of Technology (MIT) - MIT Computer Science and Artificial Intelligence Laboratory; Broad Institute of MIT and Harvard - Epigenomics Program

Douglas Ruderfer

Vanderbilt University - Medical Center

Laura G Sloofman

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

Sanne JH van Rooij

Emory University - Department of Psychiatry and Behavioral Sciences

PTSD Working Group of Psychiatric Genomics Consortium Group

Independent

Dewleen G Baker

University of California, San Diego (UCSD) - Department of Psychiatry; Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health; Veterans Affairs San Diego Healthcare System - Psychiatry Service

Chia-Yen Chen

Harvard University - Psychiatric & Neurodevelopmental Genetics Unit; Harvard University - Analytic and Translational Genetics Unit; Broad Institute of MIT and Harvard - Stanley Center for Psychiatric Research

Nancy Cox

Vanderbilt University - Medical Center

Laramie E Duncan

Stanford University - Department of Psychiatry and Behavioral Sciences

Mark A Geyer

University of California, San Diego (UCSD) - Department of Psychiatry; Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health; Veterans Affairs San Diego Healthcare System - Research Service

Stephen J. Glatt

State University of New York (SUNY) - Department of Psychiatry and Behavioral Sciences

Hae Kyung Im

University of Chicago - Section of Genetic Medicine; University of Chicago - Center for Translational Data Science

Adam X Maihofer

University of California, San Diego (UCSD) - Department of Psychiatry; Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health; Veterans Affairs San Diego Healthcare System - Research Service

Victoria B Risbrough

University of California, San Diego (UCSD) - Department of Psychiatry; Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health; Veterans Affairs San Diego Healthcare System - Research Service

Jordan W Smoller

Harvard University - Psychiatric & Neurodevelopmental Genetics Unit; Broad Institute of MIT and Harvard - Stanley Center for Psychiatric Research

Dan J Stein

University of Cape Town (UCT) - SAMRC Unit on Risk & Resilience in Mental Disorders; University of Cape Town (UCT) - Department of Psychiatry

Rachel Yehuda

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Neuroscience; James J. Peters Veterans Affairs Medical Center - Mental Health Care Center

Israel Liberzon

Texas A&M University - Department of Psychiatry and Behavioral Science

Karestan C. Koenen

Harvard University - Psychiatric & Neurodevelopmental Genetics Unit; Broad Institute of MIT and Harvard - Stanley Center for Psychiatric Research; Harvard T. H. Chan School of Public Health - Department of Epidemiology

Tanja Jovanovic

Harvard University - Psychiatric & Neurodevelopmental Genetics Unit; Broad Institute of MIT and Harvard - Stanley Center for Psychiatric Research; Harvard T. H. Chan School of Public Health - Department of Epidemiology

Manolis Kellis

Massachusetts Institute of Technology (MIT) - MIT Computer Science and Artificial Intelligence Laboratory; Massachusetts Institute of Technology and Harvard University - Epigenomics Program

Mark W Miller

National Center for PTSD at VA Boston Healthcare; Boston University - Department of Biostatistics

Silviu-Alin Bacanu

Virginia Commonwealth University (VCU) - Department of Psychiatry

Caroline M Nievergelt

University of California, San Diego (UCSD) - Department of Psychiatry; Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health; Veterans Affairs San Diego Healthcare System - Research Service

Joseph D. Buxbaum

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology; Icahn School of Medicine at Mount Sinai - Seaver Autism Center for Research and Treatment; James J. Peters Veterans Affairs Medical Center - Mental Health Care Center

Pamela Sklar

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology; Icahn School of Medicine at Mount Sinai - Seaver Autism Center for Research and Treatment; Icahn School of Medicine at Mount Sinai - Department of Neuroscience

Kerry J. Ressler

Harvard University - Department of Psychiatry

Eli A Stahl

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences; Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics; Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

Nikolaos P. Daskalakis

Icahn School of Medicine at Mount Sinai - Department of Psychiatry; Harvard University - Department of Psychiatry; Massachusetts Institute of Technology (MIT) - Computer Science and Artificial Intelligence Laboratory (CSAIL); Massachusetts Institute of Technology and Harvard University - Epigenomics Program; James J. Peters Veterans Affairs Medical Center - Mental Health Care Center

More...

Abstract

PTSD has significant genetic heritability; however, it is unclear how genetic risk influences tissue-specific gene expression. We used brain and non-brain transcriptomic imputation models to impute genetically regulated gene expression (GReX) in 9,087 PTSD-cases and 23,811 controls and identified thirteen significant GReX-PTSD associations. The results suggest substantial genetic heterogeneity between civilian and military PTSD cohorts. The top study-wide significant PTSD-association was with predicted downregulation of the Small Nuclear Ribonucleoprotein U11/U12 Subunit 35 (SNRNP35) in the BA9 region of the prefrontal cortex (PFC) in military cohorts. In peripheral leukocytes from 175 U.S. Marines, the observed PTSD differential gene expression correlated with the predicted blood GReX differences for these individuals, and deployment stress downregulated SNRNP35 expression, primarily in Marines with post-deployment PTSD. SNRNP35 is a subunit of the minor spliceosome complex and SNRNP35 knockdown in cells validated its functional importance in U12-intron splicing. Finally, mimicking acute activation of the endogenous stress axis in mice downregulated PFC Snrnp35 expression.

Suggested Citation

Huckins, Laura M. and Breen, Michael S and Chatzinakos, Chris and Hartmann, Jakob and Klengel, Torsten and da Silva Almeida, Ana C and Dobbyn, Amanda and Girdhar, Kiran and Hoffman, Gabriel E and Klengel, Claudia and Logue, Mark W and Lori, Adriana and Morrison, Filomene G and Nguyen, Hoang T and Park, Yongjin and Ruderfer, Douglas and Sloofman, Laura G and van Rooij, Sanne JH and Group, PTSD Working Group of Psychiatric Genomics Consortium and Baker, Dewleen G and Chen, Chia-Yen and Cox, Nancy and Duncan, Laramie E and Geyer, Mark A and Glatt, Stephen J. and Kyung Im, Hae and Maihofer, Adam X and Risbrough, Victoria B and Smoller, Jordan W and Stein, Dan J and Yehuda, Rachel and Liberzon, Israel and Koenen, Karestan C. and Jovanovic, Tanja and Kellis, Manolis and Miller, Mark W and Bacanu, Silviu-Alin and Nievergelt, Caroline M and Buxbaum, Joseph D. and Sklar, Pamela and Ressler, Kerry J. and Stahl, Eli A and Daskalakis, Nikolaos P., Analysis of Genetically Regulated Gene Expression Identifies a Trauma Type Specific PTSD Gene, SNRNP35 (March 15, 2019). Available at SSRN: https://ssrn.com/abstract=3353219 or http://dx.doi.org/10.2139/ssrn.3353219
This version of the paper has not been formally peer reviewed.

Laura M. Huckins (Contact Author)

Icahn School of Medicine at Mount Sinai - Department of Psychiatry ( email )

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences ( email )

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics ( email )

New York City, NY
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology ( email )

1425 Madison Ave
New York, NY 10029
United States

Michael S Breen

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Mount Sinai Health System - Seaver Autism Center for Research and Treatment

New York City, NY
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Chris Chatzinakos

Virginia Commonwealth University (VCU) - Department of Psychiatry

1200 East Broad Street
P.O. Box 980710
Richmond, VA 23298-0710
United States

Jakob Hartmann

Harvard University - Department of Psychiatry

Belmont, MA
United States

Torsten Klengel

Harvard University - Department of Psychiatry

Belmont, MA
United States

University Medical Center Goettingen - Department of Psychiatry and Psychotherapy

Goettingen
Germany

Ana C Da Silva Almeida

Biogen - Department of Biotherapeutic and Medicinal Sciences

Cambridge, MA
United States

Amanda Dobbyn

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics

New York City, NY
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

1425 Madison Ave
New York, NY 10029
United States

Kiran Girdhar

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics

New York City, NY
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

1425 Madison Ave
New York, NY 10029
United States

Gabriel E Hoffman

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

1425 Madison Ave
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics

New York City, NY
United States

Claudia Klengel

Harvard University - Department of Psychiatry

Belmont, MA
United States

Mark W Logue

National Center for PTSD at VA Boston Healthcare

Boston, MA
United States

Boston University - Department of Psychiatry

Boston, MA
United States

Boston University - Biomedical Genetics

Boston, MA
United States

Boston University - Department of Biostatistics

Boston, MA
United States

Adriana Lori

Emory University - Department of Psychiatry and Behavioral Sciences

Atlanta, GA 30322
United States

Filomene G Morrison

National Center for PTSD at VA Boston Healthcare

Boston, MA
United States

Boston University - Department of Psychiatry

Boston, MA
United States

Hoang T Nguyen

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics

New York City, NY
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

1425 Madison Ave
New York, NY 10029
United States

Yongjin Park

Massachusetts Institute of Technology (MIT) - MIT Computer Science and Artificial Intelligence Laboratory

32 Vassar Street
Cambridge, MA 02139
United States

Broad Institute of MIT and Harvard - Epigenomics Program

Cambridge, MA
United States

Douglas Ruderfer

Vanderbilt University - Medical Center

1211 Medical Center Dr
2525 West End Ave., Suite 400
Nashville, TN 37232
United States

Laura G Sloofman

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics

New York City, NY
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

1425 Madison Ave
New York, NY 10029
United States

Sanne JH Van Rooij

Emory University - Department of Psychiatry and Behavioral Sciences

Atlanta, GA 30322
United States

Dewleen G Baker

University of California, San Diego (UCSD) - Department of Psychiatry

La Jolla, CA 92161
United States

Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health

San Diego, CA
United States

Veterans Affairs San Diego Healthcare System - Psychiatry Service

San Diego, CA
United States

Chia-Yen Chen

Harvard University - Psychiatric & Neurodevelopmental Genetics Unit

Boston, MA
United States

Harvard University - Analytic and Translational Genetics Unit

Boston, MA
United States

Broad Institute of MIT and Harvard - Stanley Center for Psychiatric Research

Cambridge, MA
United States

Nancy Cox

Vanderbilt University - Medical Center

1211 Medical Center Dr
2525 West End Ave., Suite 400
Nashville, TN 37232
United States

Laramie E Duncan

Stanford University - Department of Psychiatry and Behavioral Sciences

401 Quarry Road
Stanford, CA 94304-5718
United States

Mark A Geyer

University of California, San Diego (UCSD) - Department of Psychiatry

La Jolla, CA 92161
United States

Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health

San Diego, CA
United States

Veterans Affairs San Diego Healthcare System - Research Service

San Diego, CA
United States

Stephen J. Glatt

State University of New York (SUNY) - Department of Psychiatry and Behavioral Sciences

Syracuse, NY
United States

Hae Kyung Im

University of Chicago - Section of Genetic Medicine

Chicago, IL
United States

University of Chicago - Center for Translational Data Science

Chicago, IL
United States

Adam X Maihofer

University of California, San Diego (UCSD) - Department of Psychiatry

La Jolla, CA 92161
United States

Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health

San Diego, CA
United States

Veterans Affairs San Diego Healthcare System - Research Service

San Diego, CA
United States

Victoria B Risbrough

University of California, San Diego (UCSD) - Department of Psychiatry

La Jolla, CA 92161
United States

Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health

San Diego, CA
United States

Veterans Affairs San Diego Healthcare System - Research Service

San Diego, CA
United States

Jordan W Smoller

Harvard University - Psychiatric & Neurodevelopmental Genetics Unit

Boston, MA
United States

Broad Institute of MIT and Harvard - Stanley Center for Psychiatric Research

Cambridge, MA
United States

Dan J Stein

University of Cape Town (UCT) - SAMRC Unit on Risk & Resilience in Mental Disorders

Cape Town
South Africa

University of Cape Town (UCT) - Department of Psychiatry

United States

Rachel Yehuda

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Neuroscience

New York, NY 10029
United States

James J. Peters Veterans Affairs Medical Center - Mental Health Care Center

Bronx, NY
United States

Israel Liberzon

Texas A&M University - Department of Psychiatry and Behavioral Science

Bryan, TX
United States

Karestan C. Koenen

Harvard University - Psychiatric & Neurodevelopmental Genetics Unit

Boston, MA
United States

Broad Institute of MIT and Harvard - Stanley Center for Psychiatric Research

Cambridge, MA
United States

Harvard T. H. Chan School of Public Health - Department of Epidemiology

655 Huntington Ave.
Boston, MA 02115
United States

Tanja Jovanovic

Harvard University - Psychiatric & Neurodevelopmental Genetics Unit

Boston, MA
United States

Broad Institute of MIT and Harvard - Stanley Center for Psychiatric Research

Cambridge, MA
United States

Harvard T. H. Chan School of Public Health - Department of Epidemiology

655 Huntington Ave.
Boston, MA 02115
United States

Manolis Kellis

Massachusetts Institute of Technology (MIT) - MIT Computer Science and Artificial Intelligence Laboratory

32 Vassar Street
Cambridge, MA 02139
United States

Massachusetts Institute of Technology and Harvard University - Epigenomics Program

Cambridge, MA
United States

Mark W Miller

National Center for PTSD at VA Boston Healthcare

Boston, MA
United States

Boston University - Department of Biostatistics

Boston, MA
United States

Silviu-Alin Bacanu

Virginia Commonwealth University (VCU) - Department of Psychiatry

1200 East Broad Street
P.O. Box 980710
Richmond, VA 23298-0710
United States

Caroline M Nievergelt

University of California, San Diego (UCSD) - Department of Psychiatry

La Jolla, CA 92161
United States

Veterans Affairs San Diego Healthcare System - Center for Excellence in Stress and Mental Health

San Diego, CA
United States

Veterans Affairs San Diego Healthcare System - Research Service

San Diego, CA
United States

Joseph D. Buxbaum

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

1425 Madison Ave
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Seaver Autism Center for Research and Treatment

New York City, NY
United States

James J. Peters Veterans Affairs Medical Center - Mental Health Care Center

Bronx, NY
United States

Pamela Sklar

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

1425 Madison Ave
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Seaver Autism Center for Research and Treatment

New York City, NY
United States

Icahn School of Medicine at Mount Sinai - Department of Neuroscience

New York, NY 10029
United States

Kerry J. Ressler

Harvard University - Department of Psychiatry ( email )

Eli A Stahl

Icahn School of Medicine at Mount Sinai - Department of Psychiatry

New York, NY 10025
United States

Icahn School of Medicine at Mount Sinai - Department of Genetics and Genomic Sciences

1425 Madison Avenue
New York, NY 10029
United States

Icahn School of Medicine at Mount Sinai - Pamela Sklar Division of Psychiatric Genomics

New York City, NY
United States

Icahn School of Medicine at Mount Sinai - Icahn Institute for Genomics and Multiscale Biology

1425 Madison Ave
New York, NY 10029
United States

Nikolaos P. Daskalakis

Icahn School of Medicine at Mount Sinai - Department of Psychiatry ( email )

New York, NY 10025
United States

Harvard University - Department of Psychiatry ( email )

Belmont, MA
United States

Massachusetts Institute of Technology (MIT) - Computer Science and Artificial Intelligence Laboratory (CSAIL) ( email )

Stata Center
Cambridge, MA 02142
United States

Massachusetts Institute of Technology and Harvard University - Epigenomics Program ( email )

Cambridge, MA
United States

James J. Peters Veterans Affairs Medical Center - Mental Health Care Center ( email )

Bronx, NY
United States

Click here to go to Cell.com

Paper statistics

Downloads
62
Abstract Views
1,132
PlumX Metrics