在门德尔的随机化分析中探索类变异:与"开始吸烟"相关的遗传变异实际上捕获了什么?
Zoe E Reed1,2, Robyn E Wootton1,2,3, Jasmine N Khouja1,2
1School of Psychological Science, University of Bristol, Bristol, UK.
Genetic epidemiology
|August 5, 2024
概括
吸烟行为的遗传仪器显示出与无关的特征有意想不到的关联,表明潜在的水平性. 研究人员应谨慎使用,并在基因分析中采用负控制方法.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 流行病学 流行病学
- 统计遗传学 统计遗传学
背景情况:
- 门德尔随机化 (MR) 依赖于遗传变异作为暴露的工具变量.
- 横向变性,即遗传变异通过与暴露无关的途径影响结果,可以对MR结果产生偏差.
- 了解和减轻横向类推断对于遗传研究中有效的因果推断至关重要.
研究的目的:
- 为了研究吸烟行为的遗传仪器中水平性质的程度.
- 为了识别与吸烟相关的表型,我们使用了基因仪器,这些基因仪器可能不是吸烟引起的.
- 为在遗传分析中解决横向型变异提供建议.
主要方法:
- 在英国生物库使用吸烟启动遗传仪器进行全现象关联研究 (PheWAS).
- 根据吸烟与吸烟的可信或不可信的因果关系来选择表型.
- 吸烟基因仪器与英国生物银行和ALSPAC中选定的表型的关联分析.
- 对从未吸烟者和儿童进行负对照分析.
主要成果:
- 与吸烟相关的遗传仪器与英国生物银行和ALSPAC的吸烟不合理引起的表型有关.
- 在吸烟的基因仪器和表型之间观察到关联,即使在从未吸烟的人中也是如此.
- 这些发现表明,吸烟行为遗传风险得分的水平形.
结论:
- 像吸烟这样的复杂行为特征的遗传风险得分可能会表现出横向的类.
- 使用MR和其他基因信息方法的研究人员应该意识到潜在的类效应.
- 采用负控制结果和三角化方法可以帮助减轻横向形变异产生的问题.
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