Stitziel Nathan O, Kathiresan Sekar
Cardiovascular Division, Department of Medicine, Washington University School of Medicine, Saint Louis, MO; Department of Genetics, Washington University School of Medicine, Saint Louis, MO; McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, MO.
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA.
Trends Cardiovasc Med. 2017 Jul;27(5):352-359. doi: 10.1016/j.tcm.2016.08.008. Epub 2016 Aug 26.
Identifying appropriate molecular targets is a critical step in drug development. Despite many advantages, the traditional tools of observational epidemiology and cellular or animal models of disease can be misleading in identifying causal pathways likely to lead to successful therapeutics. Here, we review some favorable aspects of human genetics studies that have the potential to accelerate drug target discovery. These include using genetic studies to identify pathways relevant to human disease, leveraging human genetics to discern causal relationships between biomarkers and disease, and studying genetic variation in humans to predict the potential efficacy and safety of inhibitory compounds aimed at molecular targets. We present some examples taken from studies of plasma lipids and coronary artery disease to highlight how human genetics can accelerate therapeutics development.
确定合适的分子靶点是药物研发中的关键一步。尽管传统的观察性流行病学工具以及疾病的细胞或动物模型有诸多优势，但在识别可能通向成功治疗方法的因果途径方面可能会产生误导。在此，我们回顾人类遗传学研究的一些有利方面，这些方面有可能加速药物靶点的发现。这些方面包括利用遗传学研究来识别与人类疾病相关的途径，借助人类遗传学来辨别生物标志物与疾病之间的因果关系，以及研究人类的基因变异以预测针对分子靶点的抑制性化合物的潜在疗效和安全性。我们列举了一些来自血脂与冠状动脉疾病研究的例子，以突出人类遗传学如何能够加速治疗方法的研发。
