STRACT
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 heroindependent 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 afunctionalDRD2promoterpolymorphism(rs12364283)tobemosthighlyassociatedwithPTSDliability[oddsratio (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-dependentindividuals.Substantialriskisobservedinamphetamine-dependentindividuals,withatleast 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).