Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity of such pharmacogenetic variation differ drastically across human populations. Here, we present PharmFreq, a global repository of pharmacogenetic frequency information that aggregates frequency data of 658 allelic variants from over 10 million individuals collected from >1200 studies across 144 countries. Most investigations were conducted in East Asian and European populations, accounting for 29.4 and 26.6% of all studies, respectively. We find that the number of studies per country and aggregated cohort size correlated significantly with population size (R = 0.55, P= 3*10-9) and country gross domestic product (R = 0.43, P= 2*10-6) with overall population coverage varying between 5% in Estonia to < 0.001% in many countries in Sub-Saharan Africa and Asia. All frequency data are openly accessible via a web-based interactive dashboard at pharmfreq.com that facilitates the exploration, visualization and analysis of country- and population-specific data and their inferred phenotypic consequences. PharmFreq thus presents a comprehensive, freely available resource for pharmacogenetic variant frequencies that can inform about ethnogeographic pharmacogenomic diversity and reveal important inequities that help to focus future research efforts into underrepresented populations.

中文翻译：

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PharmFreq：临床重要药物基因中民族地理等位基因变异的综合图谱。


药物代谢酶、药物转运蛋白以及编码人类主要组织相容性复合物的基因中的遗传多态性导致药物疗效和安全性的个体间差异。这种药物遗传学变异的范围、模式和复杂性在人群中差异很大。在这里，我们介绍了 PharmFreq，这是一个全球药物遗传学频率信息存储库，它汇总了从 144 个国家/地区的 >1200 研究中收集的 1000 多万个体的 658 个等位基因变异的频率数据。大多数调查是在东亚和欧洲人群中进行的，分别占所有研究的 29.4% 和 26.6%。我们发现，每个国家的研究数量和汇总队列规模与人口规模 （R = 0.55，P = 3*10-9） 和国家国内生产总值 （R = 0.43，P = 2*10-6） 显著相关，总体人口覆盖率在爱沙尼亚的 5% 到撒哈拉以南非洲和亚洲许多国家的 < 0.001% 之间。所有频率数据都可以通过 pharmfreq.com 基于 Web 的交互式仪表板公开访问，这有助于探索、可视化和分析国家和人群特异性数据及其推断的表型后果。因此，PharmFreq 为药物遗传学变异频率提供了一个全面的、免费可用的资源，可以了解民族地理药物基因组学多样性并揭示重要的不平等现象，这有助于将未来的研究工作集中在代表性不足的人群上。