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

Transl Psychiatry. 2016 May 24;6(5):e820. doi: 10.1038/tp.2016.69.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • African Americans / genetics
  • Amygdala / diagnostic imaging
  • Amygdala / physiopathology
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Cell Adhesion Molecules, Neuronal / genetics*
  • European Continental Ancestry Group / genetics
  • Facial Expression
  • Facial Recognition
  • Fear
  • Female
  • Functional Neuroimaging
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / physiopathology
  • Reflex, Startle / physiology
  • Stress Disorders, Post-Traumatic / diagnostic imaging
  • Stress Disorders, Post-Traumatic / genetics*
  • Stress Disorders, Post-Traumatic / physiopathology
  • Stress Disorders, Post-Traumatic / psychology
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / physiopathology
  • Thalamus / diagnostic imaging
  • Thalamus / physiopathology
  • Young Adult

Substances

  • Cell Adhesion Molecules, Neuronal
  • Histocompatibility Antigens Class I
  • ZNRD1AS gene product, human
  • neuroligin 1