TY  - JOUR
PY  - 2019//
TI  - Association of a noncoding RNA postmortem with suicide by violent means and in vivo with aggressive phenotypes
JO  - Biological psychiatry
A1  - Punzi, Giovanna
A1  - Ursini, Gianluca
A1  - Viscanti, Giovanna
A1  - Radulescu, Eugenia
A1  - Shin, Joo Heon
A1  - Quarto, Tiziana
A1  - Catanesi, Roberto
A1  - Blasi, Giuseppe
A1  - Jaffe, Andrew E.
A1  - Deep-Soboslay, Amy
A1  - Hyde, Thomas M.
A1  - Kleinman, Joel E.
A1  - Bertolino, Alessandro
A1  - Weinberger, Daniel R.
SP  - 417
EP  - 424
VL  - 85
IS  - 5
N2  - 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. <br><br>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. <br><br>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<sup>-6</sup>) and suicides by nonviolent means (n = 46; p = 1.4 × 10<sup>-6</sup>). 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. <br><br>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.<br><br>Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.<p />  <p>Language: en</p>
LA  - en
SN  - 0006-3223
UR  - http://dx.doi.org/10.1016/j.biopsych.2018.11.002
ID  - ref1
ER  -