Genetic ancestry plays a central role in population pharmacogenomics.

Affiliation

Yang HC(1)(2)(3), Chen CW(4), Lin YT(4), Chu SK(4).
Author information:
(1)Institute of Statistical Science, Academia Sinica, Taipei, Taiwan. [Email]
(2)Institute of Statistics, National Cheng Kung University, Tainan, Taiwan. [Email]
(3)Institute of Public Health, National Yang-Ming University, Taipei, Taiwan. [Email]
(4)Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.

Abstract

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/ ).