Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

Joseph A Boscarino1,2, Porat M Erlich1,3, Stuart N Hoffman4, Xiaopeng Zhang51Center for Health Research, Geisinger Clinic, Danville, PA, 2Department of Psychiatry, 3Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Department of Neurology, 5Department of Anesthesiology...

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Autores principales:	Boscarino JA, Erlich PM, Hoffman SN, Zhang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/1e135d56ec5f46a6bf9e3dfdeb3e6162
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spelling	oai:doaj.org-article:1e135d56ec5f46a6bf9e3dfdeb3e61622021-12-02T01:02:37ZHigher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment1176-63281178-2021https://doaj.org/article/1e135d56ec5f46a6bf9e3dfdeb3e61622012-03-01T00:00:00Zhttp://www.dovepress.com/higher-fkbp5-comt-chrna5-and-crhr1-allele-burdens-are-associated-with--a9550https://doaj.org/toc/1176-6328https://doaj.org/toc/1178-2021Joseph A Boscarino1,2, Porat M Erlich1,3, Stuart N Hoffman4, Xiaopeng Zhang51Center for Health Research, Geisinger Clinic, Danville, PA, 2Department of Psychiatry, 3Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Department of Neurology, 5Department of Anesthesiology, Geisinger Clinic, Danville, PA, USAObjective: The study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD) among outpatients at risk for PTSD.Methods: Diagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080), COMT (rs4680), CHRNA5 (rs16969968), and CRHR1 (rs110402) single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD.Results: In bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0&ndash;6, mean count = 2.92, standard deviation = 1.36) was associated with lifetime (t [409] = 3.430, P = 0.001) and early onset PTSD (t [409] = 4.239, P = 0.000028). In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158) and early onset PTSD (odds ratio = 2.36, P = 0.000093). Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count &times; high trauma, P = 0.026) and early onset PTSD (allele count &times; high trauma, P = 0.016) in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history.Conclusion: A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure interacts with risk allele count, such that PTSD is increased in those with higher risk allele counts and higher trauma exposures. Since the single nucleotide polymorphisms studied encompass stress circuitry and addiction biology, these findings may have implications for neuropsychiatric research and treatment.Keywords: posttraumatic stress disorder, genetic association study, single nucleotide polymorphism, risk alleles, trauma exposure, neuroticism, childhood adversityBoscarino JAErlich PMHoffman SNZhang XDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2012, Iss default, Pp 131-139 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Boscarino JA Erlich PM Hoffman SN Zhang X Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment
description	Joseph A Boscarino1,2, Porat M Erlich1,3, Stuart N Hoffman4, Xiaopeng Zhang51Center for Health Research, Geisinger Clinic, Danville, PA, 2Department of Psychiatry, 3Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Department of Neurology, 5Department of Anesthesiology, Geisinger Clinic, Danville, PA, USAObjective: The study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD) among outpatients at risk for PTSD.Methods: Diagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080), COMT (rs4680), CHRNA5 (rs16969968), and CRHR1 (rs110402) single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD.Results: In bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0&ndash;6, mean count = 2.92, standard deviation = 1.36) was associated with lifetime (t [409] = 3.430, P = 0.001) and early onset PTSD (t [409] = 4.239, P = 0.000028). In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158) and early onset PTSD (odds ratio = 2.36, P = 0.000093). Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count &times; high trauma, P = 0.026) and early onset PTSD (allele count &times; high trauma, P = 0.016) in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history.Conclusion: A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure interacts with risk allele count, such that PTSD is increased in those with higher risk allele counts and higher trauma exposures. Since the single nucleotide polymorphisms studied encompass stress circuitry and addiction biology, these findings may have implications for neuropsychiatric research and treatment.Keywords: posttraumatic stress disorder, genetic association study, single nucleotide polymorphism, risk alleles, trauma exposure, neuroticism, childhood adversity
format	article
author	Boscarino JA Erlich PM Hoffman SN Zhang X
author_facet	Boscarino JA Erlich PM Hoffman SN Zhang X
author_sort	Boscarino JA
title	Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment
title_short	Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment
title_full	Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment
title_fullStr	Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment
title_full_unstemmed	Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment
title_sort	higher fkbp5, comt, chrna5, and crhr1 allele burdens are associated with ptsd and interact with trauma exposure: implications for neuropsychiatric research and treatment
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/1e135d56ec5f46a6bf9e3dfdeb3e6162
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Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

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