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dc.contributor.authorKoenen, Karestan
dc.contributor.authorDeVivo, Immaculata
dc.contributor.authorRich-Edwards, Janet Wilson
dc.contributor.authorSmoller, Jordan W
dc.contributor.authorWright, Rosalind Jo
dc.contributor.authorPurcell, Shaun
dc.date.accessioned2011-07-12T14:36:24Z
dc.date.issued2009
dc.identifier.citationKoenen, Karestan C., Immaculata DeVivo, Janet Rich-Edwards, Jordan W. Smoller, Rosalind J. Wright, and Shaun M. Purcell. 2009. Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II. BMC Psychiatry 9:29.en_US
dc.identifier.issn1471-244Xen_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5025176
dc.description.abstractBackground: One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder. Methods and design: We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD. The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach. Discussion: Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1471-244X-9-29en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698903/pdf/en_US
dash.licenseLAA
dc.titleProtocol for Investigating Genetic Determinants of Posttraumatic Stress Disorder in Women from the Nurses' Health Study IIen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Psychiatryen_US
dash.depositing.authorKoenen, Karestan
dc.date.available2011-07-12T14:36:24Z
dash.affiliation.otherSPH^Society Human Development and Healthen_US
dash.affiliation.otherSPH^Epidemiologyen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Epidemiologyen_US
dash.affiliation.otherHMS^Psychiatry-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherSPH^Environmental+Occupational Medicine+Epien_US
dc.identifier.doi10.1186/1471-244X-9-29*
dash.contributor.affiliatedPurcell, Shaun M.
dash.contributor.affiliatedWright, Rosalind Jo
dash.contributor.affiliatedKoenen, Karestan
dash.contributor.affiliatedRich-Edwards, Janet
dash.contributor.affiliatedSmoller, Jordan


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