神经精神疾病和人类大脑结构的对抗性SNP之间的关联
Lydia M Federmann1,2, Friederike S David3, Christiane Jockwitz4,5
1Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany. l.federmann@fz-juelich.de.
Translational psychiatry
|October 2, 2024
概括
与多种神经精神疾病相关的对抗性单核酸多态 (SNP) 发现与大脑结构差异有关. 这些遗传变异也会影响基因表达和认知特征,这表明大脑疾病的复杂遗传结构.
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
- 大脑成像遗传学
背景情况:
- 全基因组关联研究 (GWAS) 确定了对抗性单核酸多态性 (SNP),其中等位基因赋予不同神经精神疾病的相反风险.
- 这些对抗性SNP的神经生物学基础,特别是它们与大脑结构的关联,仍然在很大程度上未被探索.
研究的目的:
- 调查之前识别的对抗性SNP与大脑结构表型的关联,包括皮层表面积,厚度和皮层下体积.
- 检查这些SNP之间的关系,脑组织中的基因表达,认知/行为特征,并进行探索性全脑分析.
主要方法:
- 利用大规模GWAS的大脑结构表型的总结统计数据来评估与11个对抗性SNP的关联.
- 与ENIGMA联盟关于神经精神疾病中大脑结构差异的数据进行了交叉引用.
- 分析了基因表达数据和认知/行为表现型,并在主要抑郁症患者队列中进行了基于voxel的全脑分析.
主要成果:
- 八种对抗性SNP显示出与大脑结构表型的显著关联,这些区域包括前带状皮质,胰岛和上回.
- 隐含的大脑结构表型以前与双相情感障碍,严重抑郁症和精神分裂症有关.
- 在探索性分析中,对抗性SNP与大脑组织的基因表达改变,认知/行为特征以及特定的灰色物质体积差异有关.
结论:
- 与神经精神疾病相关的多个对抗性SNP与不同的大脑结构表型有关.
- 这些发现强调了这些遗传变异在调解与精神病相关的大脑结构改变方面的潜在作用.
- 进一步的病例控制基因组成像研究是必要的,以充分阐明对抗性SNP,大脑结构和神经精神疾病之间的复杂关系.
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