The pharmacogenomic landscape in the Chinese: An analytics of pharmacogenetic variants in 206,640 individuals.

Abstract

Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity. However, these data are still lacking for the Chinese population. In this study, we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese individuals. In total, 1,577,513 variants (including 331,610 novel variants) were identified among 3,538 pharmacogenes related to 2,086 drugs. We found that the variant spectrum in the Chinese population differed among the seven major regions. Regional differences also exist among provinces in China. The average numbers of drug enzyme, transporter, and receptor variants were 258, 557, and 632, respectively. Subsequent correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer variants. Among the 16 categories of drugs, we found that nervous system, cardiovascular system, and genitourinary system/sex hormone drugs were more likely to be affected by variants of pharmacogenes. Characteristics of the variants in the enzyme, transporter, and receptor subfamilies showed specificity. To explore the clinical utility of these data, a genetic association study was conducted on 1,019 lung cancer patients. Two novel variants, AKT2 chr19:40770621 C>G and SLC19A1 chr21:46934171 A>C, were identified as novel platinum response biomarkers. Finally, a pharmacogenomic database, named the Chinese Pharmacogenomic Knowledge Base (CNPKB: http://www.cnpkb.com.cn/), was constructed to collect all the data. In summary, a pharmacogenomic landscape and database for the Chinese population were constructed in this study, which could support personalized Chinese medicine in the future.