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铁和痴呆的风险:曼德尔的随机化分析在英国生物银行

Francesco Casanova¹, Qu Tian², Janice L Atkins¹

¹Department of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK.

Journal of medical genetics

|January 8, 2024

概括

血清铁含量较高,通过转林和 (TSAT) 表示,是非阿尔茨海默病 (非AD) 和血管痴呆症的因果风险因素. 这种遗传联系在欧洲和非洲人群中观察到,并且独立于APOE ε4基因型.

科学领域:

神经科学是一个神经科学.
遗传学是一个遗传学.
流行病学流行病学

背景情况:

在痴呆症患者中经常观察到大脑铁沉积.
血清铁作为痴呆症的因果风险因素的作用尚不清楚.
这项研究调查了对血清铁生物标志物较高的遗传倾向及其与痴呆风险和灰质缩的关联.

研究的目的:

确定对血清铁生物标志物 (转氨酸和酸) 的基因倾向是否会增加痴呆的风险.
为了研究基因预测血清铁和灰质体积之间的关联.
检查TSAT和临床定义的痴呆症之间的关系,包括阿尔茨海默病,非AD痴呆症和血管痴呆症.

主要方法:

利用了来自欧洲,非洲和南亚群体的英国生物银行参与者.
采用孟德尔的随机化方法来评估基因预测血清铁 (TSAT和费里丁) 与痴呆风险之间的关联.
使用TSAT多基因评分进行非AD痴呆风险的事件时间分析,考虑竞争风险和apolipoprotein-E ε4基因型.

主要成果:

较高的基因预测TSAT与欧洲人患痴呆症的可能性增加有关,特别是非AD和血管痴呆症.
在非洲群体中也观察到高TSAT和非AD痴呆症风险之间的关联,但在南亚群体中没有.
基因预测的TSAT与特定大脑区域 (尾,尾,丘脑) 的灰质体积减少相关,并且这种效应独立于APOE ε4状态.

结论:

遗传证据支持TSAT升高与欧洲和非洲人群非AD和血管痴呆症风险之间的因果关系.
观察到TSAT与痴呆风险之间的关联独立于阿波利波蛋白-E ε4基因型.
通过TSAT显示的较高血清铁含量可能代表特定类型痴呆症的可修改风险因素.

关键词:

痴呆症是一种痴呆症.人口遗传学,人口遗传学

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