Genome Sequence Variability Predicts Drug Precautions and Withdrawals from the Market

Kye Hwa Lee; Su Youn Baik; Soo Youn Lee; Chan Hee Park; Paul J Park; Ju Han Kim

doi:10.1371/journal.pone.0162135

Genome Sequence Variability Predicts Drug Precautions and Withdrawals from the Market

PLoS One. 2016 Sep 30;11(9):e0162135. doi: 10.1371/journal.pone.0162135. eCollection 2016.

Authors

Kye Hwa Lee¹, Su Youn Baik¹, Soo Youn Lee¹, Chan Hee Park¹, Paul J Park², Ju Han Kim^{1

3}

Affiliations

¹ Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110799, Korea.
² Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America.
³ Biomedical Informatics Training and Education Center (BITEC), Seoul National University Hospital, Seoul 110744, Korea.

Abstract

Despite substantial premarket efforts, a significant portion of approved drugs has been withdrawn from the market for safety reasons. The deleterious impact of nonsynonymous substitutions predicted by the SIFT algorithm on structure and function of drug-related proteins was evaluated for 2504 personal genomes. Both withdrawn (n = 154) and precautionary (Beers criteria (n = 90), and US FDA pharmacogenomic biomarkers (n = 96)) drugs showed significantly lower genomic deleteriousness scores (P < 0.001) compared to others (n = 752). Furthermore, the rates of drug withdrawals and precautions correlated significantly with the deleteriousness scores of the drugs (P < 0.01); this trend was confirmed for all drugs included in the withdrawal and precaution lists by the United Nations, European Medicines Agency, DrugBank, Beers criteria, and US FDA. Our findings suggest that the person-to-person genome sequence variability is a strong independent predictor of drug withdrawals and precautions. We propose novel measures of drug safety based on personal genome sequence analysis.

Grants and funding

This research was supported by the grants of the Korean Health Technology R&D Project, Ministry of Health and Welfare (HI13C2164, HI16C11280000). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.