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Influence of DAP1 Genotype and Psychosocial Factors on Posttraumatic Stress Disorder in Thai Tsunami Survivors: A GxE Approach

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Open Journal of Genetics 2019年第3期9卷 65-75页

作者： Nuntika Thavichachart Prathan Rutchatajumroon Taisei Mushiroda Anchalee Prasansuklab Sookjaroen Tangwongchai Puangsoi Worakul Buranee Kanchanatawan Siriluck Suppapitiporn Atapol Sughondhabirom chutima roomruangwong Ongart Charoensook Wasun Chantratita Atsushi Takahashi Michiaki Kubo Naoyuki Kamatani Yusuke Nakamura Department of Psychiatry Faculty of Medicine Chulalongkorn University Bangkok Thailand Thailand Center of Excellence for Life Sciences (Public Organization) Ministry of Science and Technology Bangkok Thailand Laboratory for Pharmacogenetics RIKEN Center for Genomic Medicine Kanagawa Japan College of Public Health Sciences Chulalongkorn University Bangkok Thailand Center for Medical Genomics Ramathibodi Hospital Mahidol University Bangkok Thailand Laboratory for Statistical Analysis RIKEN Center for Genomic Medicine Kanagawa Japan Laboratory for Genotyping Development RIKEN Center for Genomic Medicine Kanagawa Japan Laboratory of Molecular Medicine Human Genome Center Institute of Medical Science The University of Tokyo Tokyo Japan

Background: Posttraumatic Stress Disorder (PTSD) is a psychiatric disorder found in individuals afflicted by a traumatic event including the natural disaster. “Tsunami” occurred in Andaman coast of Thailand on December 26, 2004, in which 33.6% of survivors were diagnosed as PTSD. This study aimed to explore the single nucleotide polymorphism (SNP). rs267943 genotype is located on chromosome 5 in the intron of the death-associated protein 1 (DAP1) gene and psychosocial factors for PTSD. Methods: Participants (N = 1970) were recruited from volunteers who have complete data both of DAP1 gene and psychosocial factor. Results: Using a binary logistic regression model, significant gene-environment interactions were found for the single nucleotide polymorphism (SNP) rs267943 and psychosocial factors including depression (adj. OR = 6.0, 95% CI = 4.29 - 8.39), neurotic personality (adj. OR = 2.73, 95% CI = 2.18 - 3.42), planning (adj. OR = 1.52, 95% CI = 1.20 - 1.93), use of emotional support (adj. OR = 1.32, 95% CI = 1.21 - 1.94) with statistical significant p Conclusion: This study demonstrated that GxE studies can be utilized to shed light on the origins of PTSD.

关键词： Death-Associated Protein 1 Gene (DAP1) Gene-by-Environment Interaction (GxE) Genetype Posttraumatic Stress Disorder (PTSD) Psychosocial Factors Tsunami

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Genome-Wide Association Study in Thai Tsunami Survivors Identified Risk Alleles for Posttraumatic Stress Disorder

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Open Journal of Genetics 2015年第2期5卷 43-57页

作者： Nuntika Thavichachart Taisei Mushiroda Thongchai Thavichachart Ongart Charoensook Anchalee Prasansuklab Prathan Rutchatajumroon Sookjaroen Tangwongchai Puangsoi Worakul Buranee Kanchanatawan Siriluck Suppapitiporn Atapol Sughondhabirom chutima roomruangwong Wasun Chantratita Atsushi Takahashi Michiaki Kubo Naoyuki Kamatani Yusuke Nakamura Department of Psychiatry Faculty of Medicine Chulalongkorn University Bangkok Thailand Laboratory for Pharmacogenetics RIKEN Center for Genomic Medicine Kanagawa Japan Thailand Center of Excellence for Life Sciences (Public Organization) Ministry of Science and Technology Bangkok Thailand Ph.D. Program in Clinical Biochemistry and Molecular Medicine Department of Clinical Chemistry Faculty of Allied Health Sciences Chulalongkorn University Bangkok Thailand Department of Pathology Faculty of Medicine Mahidol University Bangkok Thailand Laboratory for Statistical Analysis RIKEN Center for Genomic Medicine Kanagawa Japan Laboratory for Genotyping Development RIKEN Center for Genomic Medicine Kanagawa Japan Laboratory of Molecular Medicine Human Genome Center Institute of Medical Science The University of Tokyo Tokyo Japan

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.

关键词： Death-Associated Protein 1 Gene (DAP1) Genetics Genome-Wide Association Study (GWAS) Posttraumatic Stress Disorder (PTSD) Tsunami

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