论文标题
在制造药理学疗法的遗传仪器方面面临的挑战
Challenges in constructing genetic instruments for pharmacologic therapies
论文作者
论文摘要
编码大多数疗法靶标的基因没有稀有变体具有大效应或常见变体的变体，对反映相应疗法的药理作用的生物标志物具有中等影响。因此，为大多数疗法提供遗传目标验证是具有挑战性的。正在开发新的方法来结合编码疗法靶标的基因中的多种变异，这些变体与反映该疗法的药理作用的生物标志物弱相关，该疗法可用作遗传评分，可以用作适当的仪器变量。我们描述了一种解决这个重要问题的方法。
The genes that encode the targets of most therapies do not have rare variants with large-effect or common variants with moderate effects on the biomarker reflecting the pharmacologic action of the corresponding therapy. Therefore, providing genetic target validation for most therapies is challenging. Novel methods are being developed to combine multiple variants in the gene encoding the target of a therapy that are weakly associated with the biomarker reflecting the pharmacologic action of that therapy into a genetic score that can be used as an adequate instrumental variable. We describe one approach to solve this important problem.
