血homocysteine水平与死亡率之间的关联:孟德尔的随机化研究
Chang Kyun Choi1, Sun-Seog Kweon2, Young-Hoon Lee3
1Division of Cancer Registration and Surveillance, National Cancer Control Institute, National Cancer Center, Goyang, Korea.
Korean circulation journal
|August 10, 2023
概括
高水平的同类半素以前与心血管死亡率有关,但这项研究使用了门德尔的随机化来调查因果关系. 分析发现,同类氨酸与过早死亡之间没有因果关系.
科学领域:
- 心血管流行病学心血管流行病学
- 遗传流行病学遗传流行病学
- 代谢健康 代谢健康
背景情况:
- 在观察性研究中,高水平的homocysteine与心血管死亡率有着不一致的联系.
- 随机对照试验对同类氨酸对死亡率的影响产生了相互矛盾的结果.
研究的目的:
- 调查血homocysteine度与所有原因和心血管死亡率之间的因果关系.
- 利用门德尔的随机化 (MR) 分析来克服观察性研究的局限性.
主要方法:
- 分析了南文研究队列 (10,005名参与者).
- 观察分析采用多变量考克斯比例回归.
- 门德尔的随机化分析使用了2个阶段的最小平方回归,其中甲基酸酸减少酶 (MTHFR) 多态作为一个仪器变量.
主要成果:
- 观察分析显示,较高的同类半氨酸水平与全因和心血管死亡率的增加之间存在积极联系.
- 门德尔的随机化分析显示,基因预测的homocysteine水平与全因或心血管死亡率之间没有显著的因果关系.
结论:
- 门德尔的随机分析不支持高血类固醇蛋白在过早死亡中的因果作用.
- 这些发现表明,观察性研究中观察到的关联可能是混的或非因果的.
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