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

Kilaru, V., Iyer, S. V., Almli, L. M., Stevens, J. S., Lori, A., Jovanovic, T., et al. (2016). Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder. TRANSLATIONAL PSYCHIATRY, 6: e820. doi:10.1038/tp.2016.69.

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Kilaru, V.1, Author
Iyer, S. V.1, Author
Almli, L. M.1, Author
Stevens, J. S.1, Author
Lori, A.1, Author
Jovanovic, T.1, Author
Ely, T. D.1, Author
Bradley, B.1, Author
Binder, E. B.1, 2, Author           
Koen, N.1, Author
Stein, D. J.1, Author
Conneely, K. N.1, Author
Wingo, A. P.1, Author
Smith, A. K.1, Author
Ressler, K. J.1, Author
Affiliations:
1external, ou_persistent22              
2Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              

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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.

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Language(s): eng - English
 Dates: 2016-05-24
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000377306300005
DOI: 10.1038/tp.2016.69
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Title: TRANSLATIONAL PSYCHIATRY
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 6 Sequence Number: e820 Start / End Page: - Identifier: ISSN: 2158-3188