From pharmacogenetics to pharmaco-omics: Milestones and future directions.
From pharmacogenetics to pharmaco-omics: Milestones and future directions.
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DOI：
10.1016/j.xhgg.2022.100100
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发表时间：
2022-04-14
期刊：
影响因子：
--
通讯作者：
Kutalik Z
中科院分区：
文献类型：
--
作者：
Auwerx C;Sadler MC;Reymond A;Kutalik Z
药物遗传学的起源可以追溯到20世纪50年代，当时人们确定药物反应的个体间差异部分由遗传因素决定。从那时起，药物遗传学已经发展成为自己的领域，其动机是将已鉴定的基因-药物相互作用转化为治疗应用。尽管面临着许多挑战，我们对人类药物遗传学景观的理解已经大大提高，这要归功于来自生物化学，分子生物学，统计学和计算机科学等不同学科的工具的整合。在这篇综述中，我们讨论了药物遗传学方法的过去，现在和未来的发展，重点是三个里程碑：早期研究如何建立药物反应的遗传基础，技术进步如何使其能够评估药理学变异的全部程度，以及多维组学数据集如何提高基因和药物之间相互作用的识别，功能验证和机制理解。我们概述了新的策略，重新利用和整合来自生物库的分子和临床数据，以获得类似于从随机对照试验中获得的见解。强调增加多样性的重要性，我们设想未来的方向，为该领域铺平道路的药物遗传学的临床实施。
The origins of pharmacogenetics date back to the 1950s, when it was established that inter-individual differences in drug response are partially determined by genetic factors. Since then, pharmacogenetics has grown into its own field, motivated by the translation of identified gene-drug interactions into therapeutic applications. Despite numerous challenges ahead, our understanding of the human pharmacogenetic landscape has greatly improved thanks to the integration of tools originating from disciplines as diverse as biochemistry, molecular biology, statistics, and computer sciences. In this review, we discuss past, present, and future developments of pharmacogenetics methodology, focusing on three milestones: how early research established the genetic basis of drug responses, how technological progress made it possible to assess the full extent of pharmacological variants, and how multi-dimensional omics datasets can improve the identification, functional validation, and mechanistic understanding of the interplay between genes and drugs. We outline novel strategies to repurpose and integrate molecular and clinical data originating from biobanks to gain insights analogous to those obtained from randomized controlled trials. Emphasizing the importance of increased diversity, we envision future directions for the field that should pave the way to the clinical implementation of pharmacogenetics.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1056/nejmsr1809937
发表时间：
2019-08-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
All of Us Research Program Investigators;Denny JC;Rutter JL;Goldstein DB;Philippakis A;Smoller JW;Jenkins G;Dishman E
通讯作者：
Dishman E
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
8.8
作者：
Berkers, Gitte;van Mourik, Peter;van der Ent, Cornelis K.
通讯作者：
van der Ent, Cornelis K.
影响因子：
9.8
作者：
Amorosi, Clara J.;Chiasson, Melissa A.;Dunham, Maitreya J.
通讯作者：
Dunham, Maitreya J.