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

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 

作者机构：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 

出 版 物：《Open Journal of Genetics》 (遗传学期刊（英文）)

年 卷 期：2015年第5卷第2期

页      面：43-57页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

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

摘      要：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.