PT  - JOURNAL ARTICLE
AU  - Giovanna Punzi
AU  - Gianluca Ursini
AU  - Giovanna Viscanti
AU  - Eugenia Radulescu
AU  - Joo Heon Shin
AU  - Tiziana Quarto
AU  - Roberto Catanesi
AU  - Giuseppe Blasi
AU  - Andrew E. Jaffe
AU  - Amy Deep-Soboslay
AU  - Thomas M. Hyde
AU  - Joel E. Kleinman
AU  - Alessandro Bertolino
AU  - Daniel R. Weinberger
TI  - Association of a lincRNA <em>postmortem</em> with suicide by violent means and <em>in vivo</em> with aggressive phenotypes
AID  - 10.1101/257188
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 257188
4099  - http://biorxiv.org/content/early/2018/01/31/257188.short
4100  - http://biorxiv.org/content/early/2018/01/31/257188.full
AB  - 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.