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

By 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

Posted 31 Jan 2018
bioRxiv DOI: 10.1101/257188 (published DOI: 10.1016/j.biopsych.2018.11.002)

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.

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