@article{e9c9d5dd46c04986ba3317cc84fe74fe,
title = "Association of a Noncoding RNA Postmortem With Suicide by Violent Means and In Vivo With Aggressive Phenotypes",
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",
author = "Giovanna Punzi and Gianluca Ursini and Giovanna Viscanti and Eugenia Radulescu and Shin, {Joo Heon} and Tiziana Quarto and Roberto Catanesi and Giuseppe Blasi and Jaffe, {Andrew E.} and Amy Deep-Soboslay and Hyde, {Thomas M.} and Kleinman, {Joel E.} and Alessandro Bertolino and Weinberger, {Daniel R.}",
note = "Funding Information: This work was supported by the Lieber Institute for Brain Development and by the BrainSeq Consortium. This work was also supported by a grant by Regione Puglia, and by a “Capitale Umano ad Alta Qualificazione” grant by Fondazione con il Sud. Funding Information: This work was supported by the Lieber Institute for Brain Development and by the BrainSeq Consortium. This work was also supported by a grant by Regione Puglia, and by a ?Capitale Umano ad Alta Qualificazione? grant by Fondazione con il Sud. GP, GU, and DRW conceived the project, designed the study, and interpreted all the results. AD-S, TMH, and JEK curated the brain collection. JHS organized and performed RNA sequencing analysis. GU and AEJ organized and performed genotyping and imputation. GP and GU carried out differential expression and expression quantitative trait loci analyses, and AEJ contributed statistics. ER performed weighted gene coexpression network analysis. GP and GV together with TQ, GB, and AB organized and carried out recruitment of living subjects. GP together with GV acquired and analyzed behavioral data under the supervision of RC. GV, TQ, GB, and AB acquired functional magnetic resonance imaging data, which GV and TQ analyzed. GP, GU, and DRW drafted the manuscript, and all authors contributed to the final version of the article. We thank Qiang Chen, Ph.D., and Rahul Bharadwaj, Ph.D., for insightful discussions; the Lieber and Maltz families; and all the brave and generous families that consented for the brain donation of their deceased next of kin. The authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: {\textcopyright} 2018 Society of Biological Psychiatry",
year = "2019",
month = mar,
day = "1",
doi = "10.1016/j.biopsych.2018.11.002",
language = "English (US)",
volume = "85",
pages = "417--424",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "5",
}