School of Life Sciences, University of Westminster, London, United Kingdom.
Cambridge Precision Medicine Limited, ideaSpace, University of Cambridge Biomedical Innovation Hub, Cambridge, United Kingdom.
Annu Rev Pharmacol Toxicol. 2024 Jan 23;64:53-64. doi: 10.1146/annurev-pharmtox-030823-111731. Epub 2023 Jul 14.
The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied, selection of study participants, and methods used to collect and analyze data. To examine the representation of biogeographical populations in pharmacogenomic data sets, we describe individuals involved in gene-drug response studies from PharmGKB, a leading repository of drug-gene annotations, and showcase, a gene that metabolizes approximately 25% of all prescribed drugs. We also show how the historical underrepresentation of females in clinical trials has led to significantly more adverse drug reactions in females than in males.
个体的遗传构成与其对药物反应之间的关联被称为药物基因组学。通过了解遗传变异与药物疗效或毒性之间的关系，我们能够根据个体的基因型来优化药物治疗。药物基因组学研究历史上一直受到来自某些祖先群体和女性的人群的偏见和代表性不足的影响。这些偏见可能源于所研究的药物和适应症、研究参与者的选择以及用于收集和分析数据的方法等因素。为了研究生物地理人群在药物基因组学数据集的代表性，我们描述了 PharmGKB 中参与基因-药物反应研究的个体， PharmGKB 是一个药物-基因注释的主要存储库，以及展示了一个代谢大约 25%所有处方药的基因。我们还展示了临床试验中女性代表性不足的历史如何导致女性的药物不良反应明显多于男性。
