Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

与大多数其他精神疾病相比，创伤后应激障碍（PTSD）遗传学的特点是可发现性较低。因此，以前的遗传学研究对生物学理解的贡献是有限的。我们对 1,222,882 名欧洲血统个体（137,136 例）和 58,051 名非洲和美洲原住民血统混合个体（13,624 例）进行了全基因组关联研究的多血统荟萃分析。我们鉴定了 95 个全基因组重要位点（80 个新位点）。融合多组学方法确定了 43 个潜在因果基因，大致分为神经递质和离子通道突触调节剂（例如GRIA1、GRM8和CACNA1E）、发育、轴突引导和转录因子（例如FOXP2、EFNA5和DCC）、突触结构和功能基因（例如，PCLO、NCAM1和PDE4B）以及内分泌或免疫调节基因（例如，ESR1、TRAF3和TANK）。其他顶级基因会影响压力、免疫、恐惧和威胁相关过程，这些过程此前被认为是 PTSD 神经生物学的基础。这些发现加强了我们对与 PTSD 病理生理学相关的神经生物学系统的理解，同时也开辟了新的研究领域。