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. 2021 Jan 7;11(1):33.
doi: 10.3390/jpm11010033.

Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

Nayoung Han  1 , Jung Mi Oh  1 , In-Wha Kim  1
Affiliations

Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

Nayoung Han et al. J Pers Med. .

Abstract

For predicting phenotypes and executing precision medicine, combination analysis of single nucleotide variants (SNVs) genotyping with copy number variations (CNVs) is required. The aim of this study was to discover SNVs or common copy CNVs and examine the combined frequencies of SNVs and CNVs in pharmacogenes using the Korean genome and epidemiology study (KoGES), a consortium project. The genotypes (N = 72,299) and CNV data (N = 1000) were provided by the Korean National Institute of Health, Korea Centers for Disease Control and Prevention. The allele frequencies of SNVs, CNVs, and combined SNVs with CNVs were calculated and haplotype analysis was performed. CYP2D6 rs1065852 (c.100C>T, p.P34S) was the most common variant allele (48.23%). A total of 8454 haplotype blocks in 18 pharmacogenes were estimated. DMD ranked the highest in frequency for gene gain (64.52%), while TPMT ranked the highest in frequency for gene loss (51.80%). Copy number gain of CYP4F2 was observed in 22 subjects; 13 of those subjects were carriers with CYP4F2*3 gain. In the case of TPMT, approximately one-half of the participants (N = 308) had loss of the TPMT*1*1 diplotype. The frequencies of SNVs and CNVs in pharmacogenes were determined using the Korean cohort-based genome-wide association study.

Keywords: pharmacogenes; polymorphisms.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Single-nucleotide variants of pharmacogenes with alternative allele frequencies of more than 10% in a Korean population. Horizontal lines indicate median values.
Figure 2
Figure 2
Haplotype block map constructed by candidate single-nucleotide variations in CYP2B6. Notes: Block 1 includes rs8192709, rs8192711, rs34801721, rs2279341, rs12985017, and rs12985269; the linkage disequilibrium between two SNPs is indicated by the standardized r2 (red boxes).
Figure 3
Figure 3
Distribution of copy number variation frequencies for the copy number variation regions in a Korean population. (A) Frequencies of copy number variation regions. (B) Copy number variation frequencies of the detected copy number variation regions, divided into gains and losses.
See this image and copyright information in PMC

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