Pharmacogenomics (PGx) is an integral part of precision medicine and contributes to the maximization of drug efficacy and reduction of adverse drug event risk. Accurate information on PGx allele frequencies improves the implementation of PGx. Nonetheless, curating such information from published allele data is time and resource intensive. The limited number of allelic variants in most studies leads to an underestimation of certain alleles.

We applied the Pharmacogenomics Clinical Annotation Tool (PharmCAT) on an integrated 200K UK Biobank genetic dataset (N = 200,044). Based on PharmCAT results, we estimated PGx frequencies (alleles, diplotypes, phenotypes, and activity scores) for 17 pharmacogenes in five biogeographic groups: European, Central/South Asian, East Asian, Afro-Caribbean, and Sub-Saharan African. PGx frequencies were distinct for each biogeographic group. Even biogeographic groups with similar proportions of phenotypes were driven by different sets of dominant PGx alleles. PharmCAT also identified “no-function” alleles that were rare or seldom tested in certain groups by previous studies, e.g., SLCO1B1^∗31 in the Afro-Caribbean (3.0%) and Sub-Saharan African (3.9%) groups.

Estimated PGx frequencies are disseminated via the PharmGKB (The Pharmacogenomics Knowledgebase: www.pharmgkb.org). We demonstrate that genetic biobanks such as the UK Biobank are a robust resource for estimating PGx frequencies. Improving our understanding of PGx allele and phenotype frequencies provides guidance for future PGx studies and clinical genetic test panel design, and better serves individuals from wider biogeographic backgrounds.

药物基因组学（PGx）是精准医学的重要组成部分，有助于药物疗效的最大化和药物不良事件风险的降低。有关 PGx 等位基因频率的准确信息可改善 PGx 的实施。尽管如此，从已发表的等位基因数据中整理此类信息需要大量时间和资源。大多数研究中等位基因变异数量有限，导致某些等位基因被低估。

我们在集成的 20 万个英国生物库遗传数据集 (N = 200,044) 上应用了药物基因组学临床注释工具 (PharmCAT)。根据 PharmCAT 结果，我们估计了 5 个生物地理组中 17 个药物基因的 PGx 频率（等位基因、双倍型、表型和活性评分）：欧洲、中/南亚、东亚、非洲-加勒比和撒哈拉以南非洲。每个生物地理组的 PGx 频率是不同的。即使具有相似表型比例的生物地理群体也是由不同组的显性 PGx 等位基因驱动的。PharmCAT 还发现了以前研究中在某些群体中罕见或很少测试的“无功能”等位基因，例如加勒比非洲裔 (3.0%) 和撒哈拉以南非洲 (3.9%) 群体中的SLCO1B1 ^{* 31。}

估计的 PGx 频率通过 PharmGKB（药物基因组学知识库：www.pharmgkb.org）发布。我们证明，英国生物银行等遗传生物银行是估计 PGx 频率的强大资源。提高我们对 PGx 等位基因和表型频率的理解，为未来的 PGx 研究和临床基因测试组设计提供指导，并更好地为来自更广泛生物地理背景的个体提供服务。