title: Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Kilaru
authors.affiliation: School of Life Sciences, Manipal University, Manipal, India.
authors.forename: S V
authors.initials: SV
authors.lastname: Iyer
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Almli
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Stevens
authors.affiliation: Department of Human Genetics, Emory University, Atlanta, GA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lori
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jovanovic
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Ely
authors.affiliation: Mental Health Service Line, Department of Veterans Affairs Medical, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Bradley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.|Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: E B
authors.initials: EB
authors.lastname: Binder
authors.affiliation: 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.
authors.forename: N
authors.initials: N
authors.lastname: Koen
authors.affiliation: 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.
authors.forename: D J
authors.initials: DJ
authors.lastname: Stein
authors.affiliation: Department of Human Genetics, Emory University, Atlanta, GA, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: Conneely
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.|Mental Health Service Line, Department of Veterans Affairs Medical, Atlanta, GA, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Wingo
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Smith
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.|McLean Hospital, Harvard Medical School, Belmont, MA, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D005149:Facial Expression; D000066499:Facial Recognition; D005239:Fear; D005260:Female; D059907:Functional Neuroimaging; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D013216:Reflex, Startle / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000503:physiopathology; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D015395:Histocompatibility Antigens Class I; C112461:ZNRD1AS gene product, human; C093438:neuroligin 1