Abstract
Posttraumatic stress disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event. Multiple environmental and genetic factors can contribute to PTSD susceptibility. Since it is rare to find members of the same family afflicted by the same catastrophic event, it is not practical to determine PTSD susceptibility genes by a gene linkage analysis. A natural disaster, such as the 2004 Tsunami, provided us with a rare chance for a genetic analysis of PTSD. To identify SNPs associated with PTSD susceptibility, we conducted a genome-association study (GWAS) in Thai-Tsunami survivors. Initial phase of the study with 396 chronic PTSD patients and 457 controls, we identified top ninety SNPs (P -4), which were further assessed in the second phase with 395 chronic PTSD patients and 798 controls. Two SNPs (rs267950 and rs954406), were identified in the second phase, and subjected to fine mapping using a data set from both phases. SNP rs267943 showed the strongest association with PTSD susceptibility and was in complete linkage disequilibrium with SNP rs267950 with P = 6.15 × 10-8, OR = 1.46 and 95% CI = 1.19 - 1.79, reaching genome-wide significance. SNP rs267943 is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and, when linked to a synthetic promoter, could regulate transcription. To our knowledge, this is the first GWAS for PTSD susceptibility in an Asian population which could provide an important insight into the genetic contribution of PTSD and may lead to new treatment strategies for PTSD.
Highlights
Posttraumatic stress disorder (PTSD) is a psychiatric disorder with debilitating consequences that has gained much interest in recent years
We demonstrated that rs267943, located within death-associated protein 1 (DAP1) gene, had the strongest association with the risk of PTSD and could be a novel PTSD susceptibility gene
Our study suggested that DAP1 may play a role underlying the pathogenesis of PTSD
Summary
Posttraumatic stress disorder (PTSD) is a psychiatric disorder with debilitating consequences that has gained much interest in recent years. PTSD affects an individual after experiencing or witnessing a traumatic or life-threatening event such as major natural or man-made disasters including earthquakes, hurricanes, major floods, tsunami or wars. Individuals afflicted by PTSD can be categorized into three major groups according to their symptoms including re-experiencing, avoidance and hyperarousal. Not all individuals who experienced or witnessed a traumatic event will develop PTSD. Some may only experience PTSD-like symptoms for a short period of time. An individual is likely to be diagnosed with PTSD if the symptoms persist for longer than one month. PTSD can be further sub-categorized into two groups, acute and chronic PTSD, according to the length of time taken to resolve PTSD-related symptoms. Due to an increase in political unrests in numerous regions around the world today, it is likely that more and more people will be affected by PTSD.
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