Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
Institute of Statistics, National Cheng Kung University, Tainan, Taiwan.
Commun Biol. 2021 Feb 5;4(1):171. doi: 10.1038/s42003-021-01681-6.
Recent studies have pointed out the essential role of genetic ancestry in population pharmacogenetics. In this study, we analyzed the whole-genome sequencing data from The 1000 Genomes Project (Phase 3) and the pharmacogenetic information from Drug Bank, PharmGKB, PharmaADME, and Biotransformation. Here we show that ancestry-informative markers are enriched in pharmacogenetic loci, suggesting that trans-ancestry differentiation must be carefully considered in population pharmacogenetics studies. Ancestry-informative pharmacogenetic loci are located in both protein-coding and non-protein-coding regions, illustrating that a whole-genome analysis is necessary for an unbiased examination over pharmacogenetic loci. Finally, those ancestry-informative pharmacogenetic loci that target multiple drugs are often a functional variant, which reflects their importance in biological functions and pathways. In summary, we develop an efficient algorithm for an ultrahigh-dimensional principal component analysis. We create genetic catalogs of ancestry-informative markers and genes. We explore pharmacogenetic patterns and establish a high-accuracy prediction panel of genetic ancestry. Moreover, we construct a genetic ancestry pharmacogenomic database Genetic Ancestry PhD ( http://hcyang.stat.sinica.edu.tw/databases/genetic_ancestry_phd/ ).
最近的研究指出了遗传背景在群体药物遗传学中的重要作用。在这项研究中，我们分析了 1000 基因组计划（第 3 阶段）的全基因组测序数据和来自 Drug Bank、PharmGKB、PharmaADME 和生物转化的药物遗传学信息。我们在这里表明，遗传背景信息标记在药物遗传学位点中富集，这表明在群体药物遗传学研究中必须仔细考虑跨遗传背景的差异。遗传背景信息药物遗传学位点位于蛋白质编码和非蛋白质编码区域，这表明全基因组分析对于药物遗传学位点的无偏检验是必要的。最后，那些针对多种药物的遗传背景信息药物遗传学位点通常是功能变体，这反映了它们在生物学功能和途径中的重要性。总之，我们开发了一种用于超高维主成分分析的有效算法。我们创建了遗传背景信息标记和基因的遗传目录。我们探索了药物遗传学模式，并建立了一个高精度的遗传背景预测面板。此外，我们构建了一个遗传背景药物基因组数据库 Genetic Ancestry PhD（http://hcyang.stat.sinica.edu.tw/databases/genetic_ancestry_phd/）。
