Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Hospital Campus, 1st Floor, South Wing, Block 4, Westminster Bridge Road, London, SE1 7EH, UK.
Pharmacogenomics. 2010 Feb;11(2):215-26. doi: 10.2217/pgs.09.171.
Response to medication is highly variable, unpredictable and, at times, may be fatal. All drugs are more effective in certain groups of the population while showing no or minimal benefit in other groups. Although the current data on the subject are piecemeal, anecdotal evidence suggests that, in line with other common multifactorial traits, a myriad of genomic as well as environmental factors underpin population variability in drug response. Pharmacogenomics is the study of how variations in the human genome affect the variability in response to medication. Efforts to personalize treatment based on results from pharmacogenomics studies have the potential to increase efficacy, lower the overall cost of treatment, and decrease the incidence of adverse drug reactions, and are one of the major challenges of the modern era. The classical twin design has traditionally been used to assess the relative contribution of genetic and environmental factors to population variation in common, complex phenotypes, including drug response. Twins are not commonly regarded as providing the optimal design in genomic studies. However, we argue that, through their precise 'matching' for confounding variables (age, sex, cohort and common environmental effects), their amenability to numerous nonclassical study designs (genome-wide association studies or the role of epigenetic factors), and the availability of large, established registries worldwide, the twin model represents a flexible study design for systems-biology studies of drug response in humans. In this review, we describe the 'classical twin model' and its application in traditional pharmacogenetics studies, discuss the value of the twin design in the modern systems biology era, and highlight the potential of existing twin registries in formulating future strategies in pharmacogenomics research. We argue that the usefulness of this design goes beyond its traditional applications. Moreover, the flexibility of the model in concert with the amenability of large, established registries of twins worldwide to the collecting of new phenotypes will mean that the study of identical and nonidentical twins will play a considerable role in shaping our understanding of the important factors that underpin population variability in common, complex phenotypes, including response to medication.
药物反应具有高度可变性、不可预测性，有时甚至可能致命。所有药物在某些人群中更有效，而在其他人群中则没有效果或效果很小。尽管目前关于这个主题的数据是零散的，但轶事证据表明，与其他常见的多因素特征一样，基因组和环境因素的多样性是药物反应人群变异性的基础。药物基因组学是研究人类基因组中的变异如何影响对药物的反应变异性。基于药物基因组学研究结果进行个体化治疗的努力有可能提高疗效、降低治疗总成本、减少不良反应的发生，这是现代的主要挑战之一。传统的双胞胎设计通常用于评估遗传和环境因素对常见复杂表型（包括药物反应）人群变异的相对贡献。双胞胎通常不被认为是基因组研究的最佳设计。然而，我们认为，通过对混杂变量（年龄、性别、队列和常见环境效应）进行精确“匹配”，通过对多种非经典研究设计（全基因组关联研究或表观遗传因素的作用）的适应性，以及全球范围内大型、成熟的登记处的可用性，双胞胎模型代表了一种灵活的研究设计，用于研究人类药物反应的系统生物学。在这篇综述中，我们描述了“经典双胞胎模型”及其在传统药物遗传学研究中的应用，讨论了双胞胎设计在现代系统生物学时代的价值，并强调了现有双胞胎登记处在制定未来药物基因组学研究策略方面的潜力。我们认为，这种设计的用途不仅限于其传统应用。此外，该模型的灵活性与全球大型成熟双胞胎登记处收集新表型的适应性相结合，将意味着同卵和异卵双胞胎的研究将在塑造我们对常见复杂表型（包括对药物的反应）人群变异性的重要因素的理解方面发挥重要作用。
