研究创伤后应激障碍和神经退行性疾病之间的共同遗传结构:一个大规模的全基因组交叉特征分析
Yiming Shi1, Tao Zhao2, Lequn Peng1
1Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China.
创伤后应激障碍 (PTSD) 和神经退行性疾病 (如阿尔茨海默氏症) 之间存在遗传重叠. 这项研究确定了共享的遗传位置和新型易感基因,揭示了共同的生物机制.
科学领域:
- 神经遗传学 神经遗传学
- 精神病学基因组学 精神病学基因学
- 复杂疾病遗传学 复杂疾病遗传学
背景情况:
- 创伤后应激障碍 (PTSD) 是一种普遍存在的疾病,具有重大的全球影响.
- 新出现的证据表明,与压力相关的疾病与神经退行性疾病的风险增加之间存在联系.
- 对于PTSD与神经退行性疾病之间的关联的遗传基础尚不清楚.
研究的目的:
- 阐明PTSD和神经退行性疾病之间共享的遗传结构.
- 为了确定特定的共享基因组位置和为这种关联做出贡献的基因.
- 用大规模的全基因组关联研究数据调查多基因重叠.
主要方法:
- 利用双变因混合模型 (MiXeR) 来量化PTSD和四种神经退行性表型之间的多基因重叠.
- 采用条件/结合错误发现率 (FDR) 分析来识别共享的基因组位置.
- 进行交叉特征分析 (MTAG,CPASSOC) 和TWAS以确定新的易感基因.
主要成果:
- 在PTSD和神经退行性疾病之间观察到显著的遗传变异共享.
- 确定了15个不同的共享位点,在PTSD和阿尔茨海默病之间共享的Chr6上有一个显著的位点.
- 174个PTSD风险位与其他精神疾病有关,并确定了27个新的易感基因.
- 多基因风险评分显示了与阿尔茨海默病,多发性硬化症和帕金森病风险的剂量依赖关系.
结论:
- 这项研究揭示了PTSD和神经退行现象之间的共同遗传结构.
- 这些发现有助于我们更好地理解这些疾病之间的神经生物学联系.
- 鉴定到的遗传机制为未来对常见病理学的研究提供了基础.
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