Kunlin Zhang, Li Wang, Chengqi Cao, Gen Li, Ruojiao Fang, Ping Liu, Shu Luo, Xiangyang Zhang, Israel Liberzon
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.
This research output has an Altmetric Attention Score of 16. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 May 2018.
All research outputs
#1,973,556
of 23,299,593 outputs
Outputs from Frontiers in Psychiatry
#1,073
of 10,405 outputs
Outputs of similar age
#43,815
of 326,061 outputs
Outputs of similar age from Frontiers in Psychiatry
#42
of 175 outputs
Altmetric has tracked 23,299,593 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,405 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 326,061 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 175 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.
