A DRD2/ANNK1-COMT interaction, consisting of functional variants, confers risk of post-traumatic stress disorder in traumatized Chinese

Kunlin Zhang, Li Wang, Chengqi Cao, Gen Li, Ruojiao Fang, Ping Liu, Shu Luo, Xiangyang Zhang, Israel Liberzon

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Objective: Post-traumatic stress disorder (PTSD) is a trauma- and stress-related psychiatric syndrome that occurs after exposure to extraordinary stressors. The neurotransmitter dopamine (DA) plays important roles in neurobiological processes like reward and stress, and a link between PTSD and the dopaminergic system has been reported. Thus, the investigation of an association between PTSD and gene-gene interaction (epistasis) within dopaminergic genes could uncover the genetic basis of dopamine-related PTSD symptomatology and contribute to precision medicine. Methods: We genotyped seven single nucleotide polymorphisms (SNPs) of three dopaminergic genes DRD2/ANNK1 (rs1800497 and rs1801028), COMT (rs6269, rs4633, rs4818 and rs4680) and DBH (rs1611115), in a Chinese predominantly adult cohort that had been exposed to an earthquake (156 PTSD cases and 978 controls). Results: Statistical genetics analysis identified a DRD2/ANNK1-COMT interaction (rs1800497 × rs6269), which is associated with PTSD diagnosis (Pinteraction = 0.0008055 and Pcorrected = 0.0169155). Single-variant and haplotype-based subset analyses showed that rs1800497 modulates the association directions of both the rs6269 G allele and the rs6269-rs4633-rs4818-rs4680 haplotype G-C-G-G. The interaction (rs1800497 × rs6269) was replicated in a Chinese young female cohort (32 cases and 581 controls, Pinteraction = 0.01329). Conclusions: Rs1800497 is related to the DA receptor D2 density and rs6269-rs4633-rs4818-rs4680 haplotypes affect the catechol O-methyltransferase level and enzyme activity. Thus, the interaction was inferred to be at protein-protein and DA activity level. The genotype combinations of the two SNPs indicate a potential origin of DA homeostasis abnormalities in PTSD development.

Original languageEnglish (US)
Article number170
JournalFrontiers in Psychiatry
Volume9
Issue numberAPR
DOIs
StatePublished - Apr 30 2018

Keywords

  • DRD2/ANNK1-COMT interaction
  • Dopaminergic genes
  • Functional variants
  • Modulate
  • Post-traumatic stress disorder (PTSD)

ASJC Scopus subject areas

  • Psychiatry and Mental health

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