PTSD risk associated with a functional DRD2 polymorphism in heroin-dependent cases and controls is limited to amphetamine-dependent individuals.
- Authors
- Nelson, Elliot C; Heath, Andrew C; Lynskey, Michael T; Agrawal, Arpana; Henders, Anjali K; Bowdler, Lisa M; Todorov, Alexandre A; Madden, Pamela A F; Moore, Elizabeth; Degenhardt, Louisa; Martin, Nicholas G; Montgomery, Grant W
- Year
- 2014
- Journal
- Addiction biology
- PMID
- 23647975
- DOI
- 10.1111/adb.12062
- PMCID
- PMC3883923
Posttraumatic stress disorder (PTSD), a pathologic response to severe stress, is a common co-morbid disorder in substance-dependent individuals. Evidence from twin studies suggests that PTSD is moderately heritable. Genetic association studies to date have reported a limited number of replicated findings. We conducted a candidate gene association study in trauma-exposed individuals within the Comorbidity and Trauma Study's sample (1343 heroin-dependent cases and 406 controls from economically disadvantaged neighborhoods). After data cleaning, the 1430 single nucleotide polymorphisms (SNPs) retained for analyses provided coverage of 72 candidate genes and included additional SNPs for which association was previously reported as well as 30 ancestry-informative markers. We found a functional DRD2 promoter polymorphism (rs12364283) to be most highly associated with PTSD liability [odds ratio (OR) 1.65 (1.27-2.15); P = 1.58 × 10(-4) ]; however, this association was not significant, with a stringent Bonferroni correction for multiple comparisons. The top hits include SNPs from other dopaminergic system genes: DRD2 DRD3, TH and DBH. Additional analyses revealed that the association involving rs12364283 is largely limited to amphetamine-dependent individuals. Substantial risk is observed in amphetamine-dependent individuals, with at least one copy of this SNP [OR 2.86 (1.92-4.27); P = 2.6 × 10(-7) ]. Further analyses do not support extensive mediation of PTSD risk via self-reported impulsivity (BIS total score). These findings suggest roles for impairment in inhibitory control in the pathophysiology of PTSD and raise questions about stimulant use in certain populations (e.g. those in combat).
Greater risk for PTSD, controlling for sex and case status, is observed for individuals with amphetamine dependence and a copy of the rs12364283 G allele (N=124) than those with either AD alone (N=639) or a copy of the rs12364283 G allele alone (N=133). The odds ratios shown are for comparison to those with neither amphetamine dependence nor a copy of the rs12364283 G allele (N=852).
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External
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|---|---|---|---|---|
| Genomic risk for post-traumatic stress disorder in families densely affected with alcohol use disorders. | Saenz de Viteri S et al. | — | 2023 | → |
| Genetic Markers as Risk Factors for the Development of Impulsive-Compulsive Behaviors in Patients with Parkinson's Disease Receiving Dopaminergic Therapy. | Fedosova A et al. | — | 2021 | → |
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| Association of DRD2, 5-HTTLPR, and 5-HTTVNTR Gene Polymorphisms With Posttraumatic Stress Disorder in Tibetan Adolescents: A Case-Control Study. | Xiao Y et al. | — | 2019 | → |
| Significant association of DRD2 enhancer variant rs12364283 with heroin addiction in a Pakistani population. | Jabeen S et al. | — | 2019 | → |
| Understanding the Scientific Basis of Post-traumatic Stress Disorder (PTSD): Precision Behavioral Management Overrides Stigmatization. | Blum K et al. | — | 2019 | → |
| Biological underpinnings of trauma and post-traumatic stress disorder: focusing on genetics and epigenetics. | Ryan J et al. | — | 2016 | → |
| H4K5 histone acetylation of <i>BRG1</i> is associated with heroin administration rather than addiction. | Xu L et al. | — | 2016 | → |
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| The promise of using personalized genomic information to promote behavior change: is the debate over, or just beginning? | Graves KD et al. | — | 2014 | → |