Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23647975
TITLE
PTSD risk associated with a functional DRD2 polymorphism in heroin-dependent cases and controls is limited to amphetamine-dependent individuals.
ABSTRACT
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).
© 2013 Society for the Study of Addiction.
DATE PUBLISHED
2014 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2013/05/06
entrez 2013/05/08 06:00
pubmed 2013/05/08 06:00
medline 2015/04/22 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Heath AC Heath Andrew C AC
Lynskey MT Lynskey Michael T MT
Agrawal A Agrawal Arpana A
Henders AK Henders Anjali K AK
Bowdler LM Bowdler Lisa M LM
Todorov AA Todorov Alexandre A AA
Madden PA Madden Pamela A F PA
Moore E Moore Elizabeth E
Degenhardt L Degenhardt Louisa L
Martin NG Martin Nicholas G NG
Montgomery GW Montgomery Grant W GW
INVESTIGATORS
JOURNAL
VOLUME: 19
ISSUE: 4
TITLE: Addiction biology
ISOABBREVIATION: Addict Biol
YEAR: 2014
MONTH: Jul
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1369-1600
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Addict Biol
COUNTRY: United States
ISSNLINKING: 1355-6215
NLMUNIQUEID: 9604935
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
K05 AA017688 NIAAA NIH HHS United States
R01 DA017305 NIDA NIH HHS United States
R01 DA017305 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
Amphetamine dependence
DRD2
PTSD
association study
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Amphetamine-Related Disorders genetics
Australia genetics
Case-Control Studies genetics
Female genetics
Genetic Predisposition to Disease genetics
Heroin Dependence genetics
Humans genetics
Male genetics
Polymorphism, Single Nucleotide genetics
Receptors, Dopamine D2 genetics
Risk genetics
Stress Disorders, Post-Traumatic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 DRD2 protein, human
0 Receptors, Dopamine D2
OTHER ID's
OTHERID SOURCE
NIHMS466758 NLM
PMC3883923 NLM
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