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A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus

Molecular Psychiatry volume 18, pages 937–942 (2013)Cite this article

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Abstract

We describe the results of the first genome-wide association study (GWAS) of post-traumatic stress disorder (PTSD) performed using trauma-exposed white non-Hispanic participants from a cohort of veterans and their intimate partners (295 cases and 196 controls). Several single-nucleotide polymorphisms (SNPs) yielded evidence of association. One SNP (rs8042149), located in the retinoid-related orphan receptor alpha gene (RORA), reached genome-wide significance. Nominally significant associations were observed for other RORA SNPs in two African-American replication samples—one from the veteran cohort (43 cases and 41 controls) and another independent cohort (100 cases and 421 controls). However, only the associated SNP from the veteran African-American replication sample survived gene-level multiple-testing correction. RORA has been implicated in prior GWAS studies of psychiatric disorders and is known to have an important role in neuroprotection and other behaviorally relevant processes. This study represents an important step toward identifying the genetic underpinnings of PTSD.

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Acknowledgements

Funding for this study was provided by National Institute on Mental Health award RO1 MH079806 and a Department of Veterans Affairs Merit Review Grant awarded to MWM. MWL is funded by National Institute on Mental Health award K01 MH076100. The Detroit Neighborhood Health Study (PI: Allison Aiello) is funded by DA022720, DA022720-S1 and MH088283. KCK is funded by MH093612, MH078928, P51RR000165 and RC4MH092707. Funding for genotyping of the VA sample was provided by the VA National Center for PTSD.

Author contributions

Study concept and design: MWM, CB and MWL. Sample collection and interpretation of VA data: MWM, AFR and EJW. Genotyping of VA sample: CB and EM. Data cleaning and management of VA sample data: MWL, AFR and EJW. Analysis of VA genotype data: MWL. Sample collection and interpretation of DNHS data: SG, Aiello, DW, MU and KCK. Genotyping of DNHS data: MU and DW. Data cleaning and management of DNHS data: Aiello, GG and KCK. Analysis of DNHS genotype data: GG and KCK. Drafting and critical revision of the manuscript: MWM, CB, MWL, GG and KCK. All authors gave approval to the final manuscript.

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  1. M W Logue and C Baldwin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA

    M W Logue & C Baldwin

  2. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    M W Logue

  3. Center for Human Genetics, Boston University School of Medicine, Boston, MA, USA

    C Baldwin & E Melista

  4. Division of Child and Adolescent Psychiatry, Department of Psychiatry, Columbia University/NYSPI, New York, NY, USA

    G Guffanti

  5. National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA

    E J Wolf, A F Reardon & M W Miller

  6. Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA

    E J Wolf & M W Miller

  7. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA

    M Uddin & D Wildman

  8. Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA

    M Uddin

  9. Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA

    D Wildman

  10. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA

    S Galea & K C Koenen

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Logue, M., Baldwin, C., Guffanti, G. et al. A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus. Mol Psychiatry 18, 937–942 (2013). https://doi.org/10.1038/mp.2012.113

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