多原子方法和门德尔随机化分析确定了血液生物标志物和皮层下大脑结构体积之间的因果关系
Pritesh R Jain1, Madison Yates1, Carlos Rubin de Celis1
1Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, United States.
NeuroImage
|November 23, 2023
概括
这项研究使用了门德尔的随机化来将特定的蛋白质和代谢物与皮层下大脑体积联系起来,从而确定大脑疾病的潜在因果因素. 没有发现微生物关联.
科学领域:
- 神经遗传学 神经遗传学
- 神经成像是一种神经成像.
- 代谢学 代谢学 代谢学
背景情况:
- 皮下大脑结构的改变与神经退行性和精神疾病有关.
- 全基因组关联研究 (GWAS) 已经确定了与大脑结构相关的遗传变异.
研究的目的:
- 为了识别与皮层下大脑结构体积因果相关的蛋白质,代谢物或微生物.
- 为了利用两个样本的门德尔随机化方法进行因果推理.
主要方法:
- 利用了GWAS的数据,用于七个皮层下大脑结构 (accumbens,杏仁体,尾状体,海马体,皮体,皮体, thalamus).
- 分析了2994种血蛋白,237种代谢物和103种微生物属的遗传关联.
- 采用了一个双样本的门德尔随机化框架.
主要成果:
- 确定了11种蛋白质和6种代谢物与皮下结构体积之间的显著关联.
- 确认了accumbens体积与血蛋白酶c1抑制剂,以及putamen体积与Agouti信号蛋白之间的因果关系.
- 发现尿酸与乳头体积有很强的关联;没有检测到微生物关联.
结论:
- 研究结果表明,特定的蛋白质和代谢物在皮层下大脑体积调节中起因作用.
- 突出了与皮层下大脑结构相关的神经发育和精神疾病的潜在治疗点.
- 确定生物过程,包括蛋白质溶解和ER细胞亡信号丰富.
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