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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.
