Personalized pharmacogenomics profiling using whole-genome sequencing

Clint Mizzi, B Peters, C Mitropoulou, K Mitropoulos, T Katsila, MR Agarwal, Ron van Schaik, R Drmanac, Joseph Borg, GP Patrinos

Research output: Contribution to journalArticleAcademicpeer-review

83 Citations (Scopus)


Aim: Pharmacogenomics holds promise to rationalize drug use by minimizing drug toxicity and at the same time increase drug efficacy. There are currently several assays to screen for known pharmacogenomic biomarkers for the most commonly prescribed drugs. However, these genetic screening assays cannot account for other known or novel pharmacogenomic markers. Materials & methods: We analyzed whole-genome sequences of 482 unrelated individuals of various ethnic backgrounds to obtain their personalized pharmacogenomics profiles. Results: Bioinformatics analysis revealed 408,964 variants in 231 pharmacogenes, from which 26,807 were residing on exons and proximal regulatory sequences, whereas 16,487 were novel. In silico analyses indicated that 1012 novel pharmacogene-related variants possibly abolish protein function. We have also performed whole-genome sequencing analysis in a seven-member family of Greek origin in an effort to explain the variable response rate to acenocoumarol treatment in two family members. Conclusion: Overall, our data demonstrate that whole-genome sequencing, unlike conventional genetic screening methods, is necessary to determine an individual's pharmacogenomics profile in a more comprehensive manner, which, combined with the gradually decreasing whole-genome sequencing costs, would expedite bringing personalized medicine closer to reality.
Original languageUndefined/Unknown
Pages (from-to)1223-1234
Number of pages12
Issue number9
Publication statusPublished - 2014

Research programs

  • EMC MM-01-25-01

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