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

• Type of Material: Article
• Authors: V. Kilaru, Emory University; Shruti Iyer, Emory University; Lynn Almli, Emory University; J.S. Stevens, Emory University; Adriana Lori, Emory University; Tanja Jovanovic, Emory University; T.D. Ely, Emory University; Bekh Bradley-Davino, Emory University; Elisabeth B. Binder, Emory University; N. Koen, University of Cape Town; D.J. Stein, University of Cape Town; Karen N Conneely, Emory University; Aliza Wingo, Emory University; Alicia K Smith, Emory University; Kerry Ressler, Emory University
• Language: English
• Date: 2016-05-24
• Publisher: Nature Publishing Group: Open Access Journals - Option B
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Macmillan Publishers Limited
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/tp.2016.69
• Title of Journal or Parent Work: Translational Psychiatry
• ISSN: 2158-3188
• Volume: 6
• Issue: 5
• Start Page: e820
• End Page: e820
• Grant/Funding Information: APW was supported by the Department of Veterans Affairs Career Development Award IK2CX000601 and the NARSAD Young Investigator Award. Support for the Drakenstein study was provided by the Bill and Melinda Gates Foundation (OPP1017641).; his work was supported by the National Institutes of Mental Health (MH071537 and MH096764 to KJR; MH098212 to TJ; T32 MH87977-5 to LMA) and the Brain Behavior Research Institute (to AKS). Support was also received from Emory and Grady Memorial Hospital General Clinical Research Center, NIH National Centers for Research Resources (M01RR00039) and Howard Hughes Medical Institute (KJR).; Support was also received from the National Institute of Mental Health (NIMH) Brain Disorders in the Developing World: Research Across the Lifespan program (R21 MH098662).; DJS and NK are supported by the Medical Research Council of South Africa.
• Keywords: LATERAL AMYGDALA; Life Sciences & Biomedicine; NEGATIVE EMOTION; EXPOSURE THERAPY; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; FACE PERCEPTION; CONDITIONED FEAR EXTINCTION; D-CYCLOSERINE; INPUT SYNAPSES; PLACEBO-CONTROLLED TRIAL; Psychiatry; TRAUMA EXPOSURE; Science & Technology
• Research Categories: Psychology, Clinical; Psychology, Behavioral; Biology, Genetics

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.