ArticlePsychoneuroendocrinology2014
Stress-related genes and heroin addiction: a role for a functional FKBP5 haplotype.
Article in Psychoneuroendocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies.Molecular psychiatry · 2023Pooled it
- A non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6, is associated with heroin addiction.PloS one · 2018Trial
- The influence of stress and social defeat on neurobiological reinforcement mechanisms across reward to withdrawal in nicotine addiction.Psychopharmacology · 2025Review
- Morphine regulates astrocyte transcriptional dynamics in the ventral tegmental area by stimulation of glucocorticoid signaling.bioRxiv : the preprint server for biology · 2025Article
- Article
- Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025Review
- SNP analysis of stress-related genes reveals significant correlations with drug addiction in Jordan.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder.Nature communications · 2024Article
- Article
- Article
- Single-nucleus genomics in outbred rats with divergent cocaine addiction-like behaviors reveals changes in amygdala GABAergic inhibition.Nature neuroscience · 2023Article
- Neuroimmune Mechanisms of Opioid Use Disorder and Recovery: Translatability to Human Studies, and Future Research Directions.Neuroscience · 2023Review
- Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery.Frontiers in psychiatry · 2023Review
- Corticotropin releasing factor and drug seeking in substance use disorders: Preclinical evidence and translational limitations.Addiction neuroscience · 2022Article
- Epigenome-wide association analyses of active injection drug use.Drug and alcohol dependence · 2022Article
- The Role of the Central Amygdala in Alcohol Dependence.Cold Spring Harbor perspectives in medicine · 2021Review
- Further evidence for the association ofPharmacogenomics · 2020Article
- Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis.Genes, brain, and behavior · 2020Review
- The moderating effect of FKBP5 and 5-HTTLPR polymorphisms on the day-level association between drinking to cope motivation and negative affect.Psychiatry research · 2020Article
- Pituitary Adenylate Cyclase-Activating Peptide (PACAP) Signaling and the Dark Side of Addiction.Journal of molecular neuroscience : MN · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundStress is a critical risk factor affecting both the development of and the relapse to drug addictions. Drug addictions are caused by genetic, environmental and drug-induced factors. The objective of this hypothesis-driven association study was to determine if genetic variants in stress-related genes are associated with heroin addiction.
methods112 selected genetic variants in 26 stress-related genes were genotyped in 852 case subjects and 238 controls of predominantly European ancestry. The case subjects are former heroin addicts with a history of at least one year of daily multiple uses of heroin, treated at a methadone maintenance treatment program (MMTP). The two most promising SNPs were subsequently tested in an African-American sample comprising of 314 cases and 208 control individuals.
resultsNineteen single nucleotide polymorphisms (SNPs) in 9 genes (AVP, AVPR1A, CRHR1, CRHR2, FKBP5, GAL, GLRA1, NPY1R and NR3C2) showed nominally significant association with heroin addiction. The associations of two FKBP5 SNPs that are part of one haplotype block, rs1360780 (intron 2) and rs3800373 (the 3' untranslated region), remained significant after correction for multiple testing (Pcorrected=0.03; OR=2.35, Pcorrected=0.0018; OR=2.85, respectively). The two SNPs also showed nominally significant association (P<0.05) with heroin addiction in an independent African-American cohort. FKBP5 is a co-chaperone that regulates glucocorticoid sensitivity. These FKBP5 SNPs were previously associated with diverse affective disorders and showed functional differences in gene expression and stress response. This study also supports our and others' previous reports of association of the GAL SNP rs694066 and the AVPR1A SNPs rs11174811, rs1587097 and rs10784339 with heroin and general drug addiction, respectively.
conclusionsThis study suggests that variations in the FKBP5 gene contribute to the development of opiate addiction by modulating the stress response. These findings may enhance the understanding of the interaction between stress and heroin addiction.
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