BACKGROUND A polygenic risk score (PRS) derived from genome-wide association studies of posttraumatic stress disorder (PTSD) may inform risk for this disorder. To date, however, no known study has examined whether social environmental factors such as attachment style may moderate the relation between PRS and PTSD. METHODS We evaluated main and interactive effects of PRS and attachment style on PTSD symptoms in a nationally representative sample of trauma-exposed European-American U.S. military veterans (N = 2030). PRS was derived from a genome-wide association study of PTSD re-experiencing symptoms (N = 146,660) in the Million Veteran Program cohort. Using one-sample Mendelian randomization with data from the UK Biobank (N = 115,099), we evaluated the effects of re-experiencing PRS and attachment style on PTSD symptoms. RESULTS Higher re-experiencing PRS and secure attachment style were independently associated with PTSD symptoms. A significant PRS-by-attachment style interaction was also observed (β = -.11, p = .006), with a positive association between re-experiencing PRS and PTSD symptoms observed only among veterans with an insecure attachment style. One-sample Mendelian randomization analyses suggested that the association between PTSD symptoms and attachment style is bidirectional. PRS enrichment analyses revealed a significant interaction between attachment style and a variant mapping to the IGSF11 gene (rs151177743, p = 2.1 × 10-7), which is implicated in regulating excitatory synaptic transmission and plasticity. CONCLUSIONS Attachment style may moderate polygenic risk for PTSD symptoms, and a novel locus implicated in synaptic transmission and plasticity may serve as a possible biological mediator of this association. These findings may help inform interpersonally oriented treatments for PTSD for individuals with high polygenic risk for this disorder.

中文翻译：

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依恋方式减轻了美国退伍军人创伤后压力的多基因风险：退伍军人国家健康和复原力研究的结果

背景 源自创伤后应激障碍 (PTSD) 全基因组关联研究的多基因风险评分 (PRS) 可能会告知这种疾病的风险。然而，迄今为止，还没有已知的研究检查过依恋风格等社会环境因素是否可以调节 PRS 和 PTSD 之间的关系。方法我们评估了 PRS 和依恋风格对 PTSD 症状的主要和交互作用，这些影响是在一个具有全国代表性的暴露于创伤的欧美美国退伍军人样本（N = 2030）中。PRS 源自百万退伍军人计划队列中 PTSD 重新体验症状（N = 146,660）的全基因组关联研究。使用来自英国生物银行 (N = 115,099) 的数据的单样本孟德尔随机化，我们评估了重新体验 PRS 和依恋风格对 PTSD 症状的影响。结果 更高的再体验 PRS 和安全依恋风格与 PTSD 症状独立相关。还观察到显着的 PRS 依恋风格相互作用（β = -.11，p = .006），仅在具有不安全依恋风格的退伍军人中观察到重新体验 PRS 和 PTSD 症状之间的正相关。单样本孟德尔随机分析表明 PTSD 症状与依恋风格之间的关联是双向的。PRS 富集分析揭示了依恋类型与映射到 IGSF11 基因 (rs151177743, p = 2.1 × 10-7) 的变体之间存在显着的相互作用，这与调节兴奋性突触传递和可塑性有关。结论 依恋方式可能会减轻 PTSD 症状的多基因风险，一个与突触传递和可塑性有关的新位点可能是这种关联的生物介质。这些发现可能有助于为这种疾病的多基因风险高的个体提供以人际交往为导向的 PTSD 治疗方法。