Association of a lincRNA postmortem with suicide by violent means and in vivo with aggressive phenotypes
Joo Heon Shin,
Andrew E. Jaffe,
Thomas M. Hyde,
Joel E Kleinman,
Daniel R Weinberger
Posted 31 Jan 2018
bioRxiv DOI: 10.1101/257188 (published DOI: 10.1016/j.biopsych.2018.11.002)
Posted 31 Jan 2018
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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