Cited by 282Suicide and Self-Harm StudiesStress Responses and CortisolGenetic Associations and Epidemiology

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Interaction of FKBP5, a Stress-Related Gene, with Childhood Trauma Increases the Risk for Attempting Suicide

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Roy, Alec, Gorodetsky, Elena, Yuan, Qiaoping, Goldman, David, Enoch, Mary-Anne·2010·Neuropsychopharmacology

DOI 10.1038/npp.2009.236PMC PMC2962602

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Abstract

Childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and is a known risk factor for suicidal behavior. In this study we sought to determine whether the impact of childhood trauma on suicide risk might be modified by FKBP5, an HPA-axis regulating gene. Sixteen FKBP5 haplotype-tagging single nucleotide polymorphisms (SNPs) were genotyped in a sample of African Americans: 398 treatment-seeking patients with substance dependence (90% men; 120 suicide attempters) and 432 nonsubstance-dependent individuals (40% men; 21 suicide attempters). In all, 474 participants (112 suicide attempters) also completed the Childhood Trauma Questionnaire (CTQ). Primary haplotype analyses were conducted with the four SNPs implicated in earlier studies: rs3800373, rs9296158, rs1360780, and rs9470080. We found that childhood trauma was associated with suicide attempt (P<0.0001). Although there was no main effect of the two major yin yang haplotypes in the four SNP haplotype blocks, there was a haplotype influence on suicide risk (p=0.006) only in individuals exposed to high levels of childhood trauma. In this group, 51% with two copies of the risk haplotype, 36% with one copy, and 20% with no copies had attempted suicide. The total logistic regression model accounted for 13% of the variance in attempted suicide. Analyses of the 16 SNPs showed significant main effects on suicide attempt of rs3777747, rs4713902, and rs9470080 and interactive effects of rs3800373, rs9296158, and rs1360780 with CTQ score on suicide attempt. These data suggest that childhood trauma and variants of the FKBP5 gene may interact to increase the risk for attempting suicide.

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Authors: Roy, A., Gorodetsky, E., Yuan, Q., Goldman, D., & Enoch, M.-A.
Affiliations: VA New Jersey Health Care System (US)
National Institutes of Health (US)
Corresponding author: Roy, Alec
ORCID: Gorodetsky, Elena
Yuan, Qiaoping
Goldman, David
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2010-01-20
Volume: 35
Issue: 8
Pages: 1674-1683
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/npp.2009.236
PMC: PMC2962602
OpenAlex: W2043313558
Cited by: 282
References: 73
Citations by year: 2025: 8 · 2024: 1 · 2023: 12 · 2022: 7 · 2021: 22 · 2020: 15 · 2019: 17 · 2018: 34 · 2017: 18 · 2016: 28 · 2015: 30 · 2014: 26 · 2013: 21 · 2012: 18
FWCI: 22.42
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (Z99‐AA999999)
National Institute on Alcohol Abuse and Alcoholism (Z01AA000301, ZIAAA000306)
National Institute on Drug Abuse (R01DA010336)
Topics: Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: FKBP5, childhood trauma, suicide attempts, gene-environment interaction, HPA axis dysregulation, single nucleotide polymorphisms, haplotypes, substance dependence, African Americans, stress-related genes
MeSH terms: Tacrolimus Binding Protein 5, Adult, Black or African American, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, New Jersey, Surveys and Questionnaires, Risk Factors, Suicide, Attempted, Linkage Disequilibrium, Computational Biology, Substance-Related Disorders, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins, Adult Survivors of Child Abuse, Young Adult

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Interaction of FKBP5, a Stress-Related Gene, with Childhood Trauma Increases the Risk for Attempting Suicide

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