Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women

Guia Guffanti, Sandro Galea, Lulu Yan, Andrea L. Roberts, Nadia Solovieff, Allison E. Aiello, Jordan W. Smoller, Immaculata De Vivo, Hardeep Ranu, Monica Uddin, Derek E. Wildman, Shaun Purcell, Karestan C. Koenen

Research output: Contribution to journalArticle

Abstract

Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder's genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII).We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for >700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions. We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences.

Original languageEnglish (US)
Pages (from-to)3029-3038
Number of pages10
JournalPsychoneuroendocrinology
Volume38
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • GWAS
  • Immune system
  • LincRNA
  • PTSD
  • Telomere maintenance

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

Fingerprint Dive into the research topics of 'Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women'. Together they form a unique fingerprint.

  • Cite this

    Guffanti, G., Galea, S., Yan, L., Roberts, A. L., Solovieff, N., Aiello, A. E., Smoller, J. W., De Vivo, I., Ranu, H., Uddin, M., Wildman, D. E., Purcell, S., & Koenen, K. C. (2013). Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women. Psychoneuroendocrinology, 38(12), 3029-3038. https://doi.org/10.1016/j.psyneuen.2013.08.014