Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Nat Biotechnol. 2012 Nov;30(11):1117-24. doi: 10.1038/nbt.2424. Epub 2012 Nov 8.
Genome-wide association studies (GWAS) of responses to drugs, including clopidogrel, pegylated-interferon and carbamazepine, have led to the identification of specific patient subgroups that benefit from therapy. However, the identification and replication of common sequence variants that are associated with either efficacy or safety for most prescription medications at odds ratios (ORs) >3.0 (equivalent to >300% increased efficacy or safety) has yet to be translated to clinical practice. Although some of the studies have been completed, the results have not been incorporated into therapy, and a large number of commonly used medications have not been subject to proper pharmacogenomic analysis. Adoption of GWAS, exome or whole genome sequencing by drug development and treatment programs is the most striking near-term opportunity for improving the drug candidate pipeline and boosting the efficacy of medications already in use.
药物反应的全基因组关联研究(GWAS),包括氯吡格雷、聚乙二醇干扰素和卡马西平,已经确定了从治疗中受益的特定患者亚组。然而,对于大多数处方药,识别和复制与疗效或安全性相关的常见序列变异,其比值比(OR)>3.0(相当于疗效或安全性增加>300%),尚未转化为临床实践。尽管一些研究已经完成,但结果尚未纳入治疗,并且大量常用药物尚未进行适当的药物基因组学分析。药物开发和治疗计划采用 GWAS、外显子组或全基因组测序,是改善候选药物管道和提高现有药物疗效的最显著的近期机会。