Abstract
Medication safety and efficacy-related pharmacogenomic research play a critical role in precision medicine. This study comprehensively analyzed the pharmacogenomic profiles of the central Han Chinese population in the context of medication safety and efficacy and compared them with other global populations. The ultimate goal is to improve medical treatment guidelines. We performed whole-genome sequencing in 487 Han Chinese individuals and investigated the allele frequencies of pharmacogenetic variants in 1,731 drug response-related genes. We identified 2,139 (81.18%) previously reported variants in our population with annotations in the PharmGKB database. The allele frequencies of these 2,139 clinical-related variants were similar to those in other East Asian populations but different from those in other global populations. We predicted the functional effects of nonsynonymous variants in the 1,731 pharmacogenes and identified 1,281 novel and 4,442 previously reported deleterious variants. Of the 1,281 novel deleterious variants, five are common variants with an allele frequency >5%, and the rest are rare variants with an allele frequency <5%. Of the 4,442 known deleterious variants, the allele frequencies were found to differ from those in other populations, of which 146 are common variants. In addition, we found many variants in non-coding regions, the functions of which require further investigation. This study compiled a large amount of data on pharmacogenomic variants in the central Han Chinese population. At the same time, it provides insight into the role of pharmacogenomic variants in clinical medication safety and efficacy.
Highlights
Clinical medication efficacy and adverse drug reactions (ADRs) often vary widely among individuals
The allele frequencies of 14 of these 16 variants were significantly different from those in the global populations included in the 1000 genomes project phase 3 (1KG3) and genome Aggregation Database (gnomAD) databases (Figure 2, Supplementary Table S2)
The allele frequencies of pharmacogenomic markers of drug efficacy and toxicity vary among ethnicities (Ramos et al, 2014)
Summary
Clinical medication efficacy and adverse drug reactions (ADRs) often vary widely among individuals. Traditional methods to detect drug reaction-related genetic polymorphisms include PCR and microarray-based techniques (Hodel et al, 2009; Burmester et al, 2010). These methods are cost-effective and easy to implement, they focus on the most common pharmacogenomic variants rather than identifying novel or rare polymorphisms associated with individual differences in drug responses. Relevant variants, in terms of drug efficacy and adverse effects, vary widely in frequency among global populations (Yasuda et al, 2008; Ramos et al, 2014). Qi et al (2020b) assessed the genetic variations in 57 CYP and cytochrome P450 oxidoreductase genes in a large-scale WGS study based on the Chinese Millionome database; the shallow sequencing depth may have led to rare variants being missed. To the best of our knowledge, this is the first comprehensive pharmacogenomic study conducted in a Chinese population
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