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Transl Psychiatry. 2016 May 24;6:e820. doi: 10.1038/tp.2016.69.

Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder.

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Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
School of Life Sciences, Manipal University, Manipal, India.
Department of Human Genetics, Emory University, Atlanta, GA, USA.
Mental Health Service Line, Department of Veterans Affairs Medical, Atlanta, GA, USA.
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Department of Psychiatry, University of Cape Town, Cape Town, South Africa.
Department of Psychiatry and MRC Unit on Anxiety and Stress Disorders, University of Cape Town, Cape Town, South Africa.
McLean Hospital, Harvard Medical School, Belmont, MA, USA.


Post-traumatic stress disorder (PTSD) develops in only some people following trauma exposure, but the mechanisms differentially explaining risk versus resilience remain largely unknown. PTSD is heritable but candidate gene studies and genome-wide association studies (GWAS) have identified only a modest number of genes that reliably contribute to PTSD. New gene-based methods may help identify additional genes that increase risk for PTSD development or severity. We applied gene-based testing to GWAS data from the Grady Trauma Project (GTP), a primarily African American cohort, and identified two genes (NLGN1 and ZNRD1-AS1) that associate with PTSD after multiple test correction. Although the top SNP from NLGN1 did not replicate, we observed gene-based replication of NLGN1 with PTSD in the Drakenstein Child Health Study (DCHS) cohort from Cape Town. NLGN1 has previously been associated with autism, and it encodes neuroligin 1, a protein involved in synaptogenesis, learning, and memory. Within the GTP dataset, a single nucleotide polymorphism (SNP), rs6779753, underlying the gene-based association, associated with the intermediate phenotypes of higher startle response and greater functional magnetic resonance imaging activation of the amygdala, orbitofrontal cortex, right thalamus and right fusiform gyrus in response to fearful faces. These findings support a contribution of the NLGN1 gene pathway to the neurobiological underpinnings of PTSD.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

SB is a consultant for Myriad Genetics and a director for Psynova Neurotech. The remaining authors declare no conflict of interest.

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