Background

The G allele in retinoid-related orphan receptor alpha (RORA, rs8042149) gene is associated with post-traumatic stress disorder (PTSD) diagnosis and more severe symptoms, reported in the first genome-wide association study of PTSD and subsequent replication studies. Although recent MRI studies identified brain structural deficits in RORA rs8042149 risk G allele carriers, the neural mechanism underlying RORA–related brain structural changes in PTSD remains poorly understood.

Methods

This study included 227 Han Chinese adults who lost their only child. Cortical thickness and subcortical volume were extracted using FreeSurfer, and PTSD severity was assessed using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to assess the interaction effect between RORA genotypes (T/T, G/T, and G/G) and PTSD severity on cortical and subcortical structures.

Results

Significant genotype × PTSD symptom severity interaction effects were found for bilateral transverse temporal gyrus thickness. For individuals with the homozygous T/T genotype, current PTSD symptom severity was positively associated with bilateral transverse temporal gyrus thickness. For individuals with heterozygous G/T genotype, current PTSD symptom severity was negatively associated with the left transverse temporal gyrus thickness. No significant main or interaction effects were found in any subcortical regions.

Limitation

Cross-sectional design of this study.

Conclusion

These findings suggest that the non-risk T/T genotype – but not the risk G allele carriers – has a potentially protective or compensatory role on temporal gyrus thickness in adults who lost their only child. These results highlight the moderation effect of RORA polymorphism on the relationship between PTSD symptom severity and cortical structural changes.

中文翻译：

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RORA rs8042149 多态性调节失去独生子女的汉族成年人 PTSD 症状严重程度与颞横回厚度之间的关联

背景

类视黄醇相关孤儿受体 α (RORA, rs8042149) 基因中的 G 等位基因与创伤后应激障碍 (PTSD) 诊断和更严重的症状相关，这在第一次 PTSD 的全基因组关联研究和随后的复制研究中得到了报道。尽管最近的 MRI 研究确定了 RORA rs8042149 风险 G 等位基因携带者的脑结构缺陷，但对RORA相关的 PTSD 脑结构变化的神经机制仍然知之甚少。

方法

这项研究包括 227 名失去独生子女的汉族成年人。使用 FreeSurfer 提取皮质厚度和皮质下体积，并使用临床医生管理的 PTSD 量表评估 PTSD 严重程度。分层线性回归用于评估RORA基因型（T/T、G/T 和 G/G）与 PTSD 严重程度对皮质和皮质下结构的交互作用。

结果

对于双侧颞横回厚度，发现了显着的基因型 × PTSD 症状严重程度相互作用效应。对于具有纯合 T/T 基因型的个体，当前的 PTSD 症状严重程度与双侧颞横回厚度呈正相关。对于具有杂合 G/T 基因型的个体，当前的 PTSD 症状严重程度与左侧颞横回厚度呈负相关。在任何皮层下区域均未发现显着的主效应或交互效应。

局限性

本研究的横断面设计。

结论

这些发现表明，非风险 T/T 基因型——但不是风险 G 等位基因携带者——对失去独生子女的成年人的颞回厚度具有潜在的保护或补偿作用。这些结果突出了RORA多态性对 PTSD 症状严重程度与皮质结构变化之间关系的调节作用。