An OXTR-DRD2 interaction (rs2268498 × rs1801028) was identified to confer risk of provisional PTSD diagnosis (OR = 9.18, 95% CI = 3.07-27.46 and P = 7.37e-05) and further subset analysis indicated that rs2268498 genotypes controlled the association directions of rs1801028 and rs1801028 genotypes also controlled the association directions of rs2268498.
<b>Results:</b> Statistical genetics analysis identified a <i>DRD2/ANNK1</i>-<i>COMT</i> interaction (rs1800497 × rs6269), which is associated with PTSD diagnosis (<i>P</i><sub>interaction</sub> = 0.0008055 and <i>P</i><sub>corrected</sub> = 0.0169155).
Further analyses revealed that this patient subset had high rates of post-traumatic stress disorder (PTSD), and enrichment in several distinct genetic polymorphisms associated with cellular responses to stress and DNA damage (PARP1), and in striatal dopamine processing (ANKK1, COMT, DRD2).
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.
Neither the DRD2 nor the DAT polymorphisms explained the variation seen in PTSD diagnosis, total PTSD symptom severity, and categories B and C symptom severities.
The DRD2 A1 allele may prove to be a useful marker to assist clinicians in predicting which patients with PTSD are likely to obtain improvements in social functioning with paroxetine treatment.
Although less intensively studied than substance use disorders, the DRD2 gene has been implicated in Tourette's syndrome (TS), post-traumatic stress disorder (PTSD) and certain symptoms associated with affective disorders and schizophrenia.
We conclude that DRD2 alleles are not associated with PTSD in this sample, and that genetic variation at the DRD2 locus is not likely to be an important contributor to risk for this disorder.
These results suggest that a DRD2 variant in linkage disequilibrium with the D2A1 allele confers an increased risk to PTSD, and the absence of the variant confers a relative resistance to PTSD.