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Biol Psychiatry. 2019 Mar 1;85(5):417-424. doi: 10.1016/j.biopsych.2018.11.002. Epub 2018 Nov 16.

Association of a Noncoding RNA Postmortem With Suicide by Violent Means and In Vivo With Aggressive Phenotypes.

Author information

1
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland; Section of Forensic Psychiatry and Criminology, Institute of Legal Medicine, Interdisciplinary Department of Medicine, Bari, Italy; Group of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy.
2
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland; Group of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy.
3
Group of Psychiatric Neuroscience, Department of Basic Medical Science, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy.
4
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland.
5
Section of Forensic Psychiatry and Criminology, Institute of Legal Medicine, Interdisciplinary Department of Medicine, Bari, Italy.
6
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
7
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland.
8
Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland; McKusick Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: drweinberger@libd.org.

Abstract

BACKGROUND:

Previous findings suggest that differences in brain expression of a human-specific long intergenic noncoding RNA (LINC01268; GRCh37/hg19: LOC285758) may be linked to suicide by violent methods. We sought to replicate and extend these findings in a new sample and translate the results to the behavioral level in living healthy subjects.

METHODS:

We examined RNA sequencing data in human brains to confirm the prior postmortem association of the long intergenic noncoding RNA specifically with suicide by violent means. In addition, we used a genetic variant associated with LINC01268 expression to detect association in healthy subjects with trait aggression and with in vivo prefrontal physiology related to behavioral control. Finally, we performed weighted gene coexpression network analysis and gene ontology analysis to identify biological processes associated with a LINC01268 coexpression network.

RESULTS:

In the replication sample, prefrontal expression of LINC01268 was again higher in suicides by violent means (n = 65) than in both nonsuicides (n = 78; p = 1.29 × 10-6) and suicides by nonviolent means (n = 46; p = 1.4 × 10-6). In the living cohort, carriers of the minor allele of a single nucleotide polymorphism associated with increased LINC01268 expression in brain scored higher on a lifetime aggression questionnaire and show diminished engagement of prefrontal cortex (Brodmann area 10) when viewing angry faces during functional magnetic resonance imaging. Weighted gene coexpression network analysis 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.

KEYWORDS:

Aggression; Brain; Postmortem; RNA-seq; Suicide; Suicide methods

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