Assessing the capability of massively parallel sequencing for opportunistic pharmacogenetic screening

Genet Med. 2017 Mar;19(3):357-361. doi: 10.1038/gim.2016.105. Epub 2016 Aug 18.


Purpose: The aim of the study was to assess exome data for preemptive pharmacogenetic screening for 203 clinically relevant pharmacogenetic variant positions from the Pharmacogenomics Knowledgebase and Clinical Pharmacogenetics Implementation Consortium and identify copy-number variants (CNVs) in CYP2D6.

Methods: We examined the coverage and genotype quality of 203 pharmacogenetic variant positions in 973 exomes compared with five genomes and with five genotyping chip data sets. Then, we determined the agreement of exome and chip genotypes by evaluating concordance in a three-way comparison of exome, genome, and chip-based genotyping at 1,929 variant positions in five individuals. Finally, we evaluated the utility of exomes for detecting CYP2D6 CNVs.

Results: For 5 individuals examined for 203 pharmacogenetic variants (5 × 203 = 1,015), 998/1,015 were identified by genome, 849/1,015 were identified by exome, and 295/1,015 by genotyping chip. Thirty-six pharmacogenetic star allele variants with moderate to strong Clinical Pharmacogenetics Implementation Consortium (CPIC) therapeutic recommendations were identified in 973 exomes. Exomes had high (98%) genotype concordance with chip-based genotyping. CYP2D6 CNVs were identified in 57/973 exomes.

Conclusions: Exomes outperformed the current chip-based assay in detecting more important pharmacogenetic variant positions and CYP2D6 CNVs for preemptive pharmacogenetic screening. Tools should be developed to derive pharmacogenetic variants from exomes.Genet Med 19 3, 357-361.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Alleles
  • Cytochrome P-450 CYP2D6 / genetics
  • DNA Copy Number Variations
  • Exome
  • Genotype
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Oligonucleotide Array Sequence Analysis / methods*
  • Pharmacogenetics
  • Pharmacogenomic Testing / methods*


  • Cytochrome P-450 CYP2D6