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Confirmatory Results

Association of a lincRNA postmortem with suicide by violent means and in vivo with aggressive phenotypes

Giovanna Punzi, Gianluca Ursini, Giovanna Viscanti, Eugenia Radulescu, Joo Heon Shin, Tiziana Quarto, Roberto Catanesi, Giuseppe Blasi, Andrew E. Jaffe, Amy Deep-Soboslay, Thomas M. Hyde, Joel E. Kleinman, Alessandro Bertolino, Daniel R. Weinberger
doi: https://doi.org/10.1101/257188
Giovanna Punzi
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
bSection of Forensic Psychiatry and Criminology, Institute of Legal Medicine, D.I.M., University of Bari ‘Aldo Moro’, Bari, Italy
cGroup of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy
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Gianluca Ursini
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
cGroup of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy
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Giovanna Viscanti
cGroup of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy
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Eugenia Radulescu
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
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Joo Heon Shin
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
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Tiziana Quarto
cGroup of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy
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Roberto Catanesi
bSection of Forensic Psychiatry and Criminology, Institute of Legal Medicine, D.I.M., University of Bari ‘Aldo Moro’, Bari, Italy
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Giuseppe Blasi
cGroup of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy
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Andrew E. Jaffe
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
dDepartment of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
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Amy Deep-Soboslay
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
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Thomas M. Hyde
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
eDepartments of Psychiatry and Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
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Joel E. Kleinman
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
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Alessandro Bertolino
cGroup of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy
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Daniel R. Weinberger
aLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA
eDepartments of Psychiatry and Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
fDepartments of Neuroscience, and the McKusick Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
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  • For correspondence: drweinberger@libd.org
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ABSTRACT

Objective Previous findings suggest that differences in brain expression of a human-specific long intergenic non-coding RNA (LINC01268; GRCh37/hg19: LOC285758) may be linked to aggressive behavior and suicide. The authors sought to replicate and extend these findings in a new sample, and translate the results to the behavioral level in living healthy subjects.

Method The authors examined RNA sequencing data in human brain to confirm the prior postmortem association of the lincRNA specifically with suicide by violent means. In addition, they used a genetic variant associated with LINC01268 expression to detect association with in vivo prefrontal physiology related to behavioral control. They finally performed weighted gene co-expression network analysis (WGCNA) and gene-ontology analysis to identify biological processes associated with a LINC01268 co-expression network.

Results In the replication sample, prefrontal expression of LINC01268 was again higher in suicides by violent means (N=65) than both non-suicides (N=78; 1.29e-06) and suicides by non-violent means (N=46; p=1.4e-06). In a living cohort, carriers of the minor allele of a SNP associated with increased LINC01268 expression in brain scored higher on a lifetime aggression questionnaire and show diminished engagement of prefrontal cortex (BA10) when viewing angry faces during fMRI. WGCNA highlighted the immune response.

Conclusions These results suggest that LINC01268 influences emotional regulation, aggressive behavior and suicide by violent means; the underlying biological dynamics may include modulation of genes potentially engaged in the immune response.

Footnotes

  • Supported by the Lieber Institute for Brain Development.

  • The Authors report no financial relationships with commercial interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 31, 2018.
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Association of a lincRNA postmortem with suicide by violent means and in vivo with aggressive phenotypes
Giovanna Punzi, Gianluca Ursini, Giovanna Viscanti, Eugenia Radulescu, Joo Heon Shin, Tiziana Quarto, Roberto Catanesi, Giuseppe Blasi, Andrew E. Jaffe, Amy Deep-Soboslay, Thomas M. Hyde, Joel E. Kleinman, Alessandro Bertolino, Daniel R. Weinberger
bioRxiv 257188; doi: https://doi.org/10.1101/257188
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Association of a lincRNA postmortem with suicide by violent means and in vivo with aggressive phenotypes
Giovanna Punzi, Gianluca Ursini, Giovanna Viscanti, Eugenia Radulescu, Joo Heon Shin, Tiziana Quarto, Roberto Catanesi, Giuseppe Blasi, Andrew E. Jaffe, Amy Deep-Soboslay, Thomas M. Hyde, Joel E. Kleinman, Alessandro Bertolino, Daniel R. Weinberger
bioRxiv 257188; doi: https://doi.org/10.1101/257188

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