Posttraumatic stress disorder (PTSD) after exposure to a traumatic event is a highly prevalent psychiatric disorder. Heritability estimates from twin studies as well as from recent molecular data (single nucleotide polymorphism-based heritability) indicate moderate to high heritability, yet robust genetic variants for PTSD have not yet been identified and the genetic architecture of this polygenic disorder remains largely unknown. To date, fewer than 10 large-scale genome-wide association studies of PTSD have been published, with findings that highlight the unique challenges for PTSD genomics, including a complex diagnostic entity with contingency of PTSD diagnosis on trauma exposure and the large genetic diversity of the study populations. The Psychiatric Genomics Consortium PTSD group has brought together more than 200 scientists with the goal to increase sample size for genome-wide association studies and other genomic analyses to sufficient numbers where robust discoveries of molecular signatures can be achieved. The sample currently includes more than 32,000 PTSD cases and 100,000 trauma-exposed control subjects, and collection is ongoing. The first results found a significant shared genetic risk of PTSD with other psychiatric disorders and sex-biased heritability estimates with higher heritability in female individuals compared with male individuals. This review describes the scope and current focus of the Psychiatric Genomics Consortium PTSD group and its expansion from the initial genome-wide association study group to nine working groups, including epigenetics, gene expression, imaging, and integrative systems biology. We further briefly outline recent findings and future directions of "omics"-based studies of PTSD, with the ultimate goal of elucidating the molecular architecture of this complex disorder to improve prevention and intervention strategies.

中文翻译：

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创伤后应激障碍的基因组学方法：精神病学基因组联盟倡议

暴露于创伤事件后的创伤后应激障碍 (PTSD) 是一种非常普遍的精神疾病。来自双胞胎研究以及最近的分子数据（基于单核苷酸多态性的遗传力）的遗传力估计表明中等至高度的遗传力，但尚未确定 PTSD 的强大遗传变异，并且这种多基因疾病的遗传结构在很大程度上仍然未知。迄今为止，已发表的 PTSD 的大规模全基因组关联研究不到 10 项，其发现突出了 PTSD 基因组学面临的独特挑战，包括复杂的诊断实体，具有创伤暴露时 PTSD 诊断的偶然性，以及研究人群。精神病基因组学联盟 PTSD 小组聚集了 200 多名科学家，目标是将全基因组关联研究和其他基因组分析的样本量增加到足够多的数量，从而实现分子特征的有力发现。该样本目前包括超过 32,000 名 PTSD 病例和 100,000 名遭受创伤的对照受试者，并且正在收集中。第一个结果发现 PTSD 与其他精神疾病具有显着的共同遗传风险，并且与男性个体相比，女性个体的遗传性估计具有更高的性别偏见。这篇综述描述了精神病基因组学联盟 PTSD 小组的范围和当前的重点，以及它从最初的全基因组关联研究小组扩展到九个工作组，包括表观遗传学、基因表达、成像和综合系统生物学。我们进一步简要概述了基于“组学”的 PTSD 研究的最新发现和未来方向，最终目标是阐明这种复杂疾病的分子结构，以改进预防和干预策略。