A Genome-Wide Association Study Identifies a Candidate Gene Associated With Atazanavir Exposure Measured in Hair

Bani Tamraz; Yong Huang; Audrey L. French; Seble Kassaye; Kathryn Anastos; Marek J. Nowicki; Stephen Gange; Deborah R. Gustafson; Peter Bacchetti; Ruth M. Greenblatt; Pirro G. Hysi; Bradley E. Aouizerat

doi:10.1002/cpt.1014

A Genome-Wide Association Study Identifies a Candidate Gene Associated With Atazanavir Exposure Measured in Hair

Bani Tamraz, Yong Huang, Audrey L. French, Seble Kassaye, Kathryn Anastos, Marek J. Nowicki, Stephen Gange, Deborah R. Gustafson, Peter Bacchetti, Ruth M. Greenblatt, Pirro G. Hysi, Bradley E. Aouizerat

Medicine

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Abstract

Hair provides a direct measure of long-term exposure of atazanavir (ATV). We report the results of the first genome-wide association study (GWAS) of ATV exposure measured in hair in an observational cohort representative of US women living with HIV; the Women's Interagency HIV Study. Approximately 14.1 million single nucleotide polymorphisms (SNPs) were analyzed in linear regression-based GWAS, with replication, adjusted for nongenetic predictors collected under conditions of actual use of ATV in 398 participants. Lastly, the PharmGKB database was used to identify pharmacogene associations with ATV exposure. The rs73208473, within intron 1 of SORCS2, resulted in a 0.46-fold decrease in ATV exposure, with the strongest association (P = 1.71×10⁻⁸) in GWAS. A priori pharmacogene screening did not identify additional variants statistically significantly associated with ATV exposure, including those previously published in ATV plasma candidate pharmacogene studies. The findings demonstrate the potential value of pharmacogenomic GWAS in ethnically diverse populations under conditions of actual use.

Original language	English (US)
Pages (from-to)	949-956
Number of pages	8
Journal	Clinical Pharmacology and Therapeutics
Volume	104
Issue number	5
DOIs	https://doi.org/10.1002/cpt.1014
State	Published - Nov 2018

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cpt.1014

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Tamraz, B., Huang, Y., French, A. L., Kassaye, S., Anastos, K., Nowicki, M. J., Gange, S., Gustafson, D. R., Bacchetti, P., Greenblatt, R. M., Hysi, P. G., & Aouizerat, B. E. (2018). A Genome-Wide Association Study Identifies a Candidate Gene Associated With Atazanavir Exposure Measured in Hair. Clinical Pharmacology and Therapeutics, 104(5), 949-956. https://doi.org/10.1002/cpt.1014

Tamraz, B, Huang, Y, French, AL, Kassaye, S, Anastos, K, Nowicki, MJ, Gange, S, Gustafson, DR, Bacchetti, P, Greenblatt, RM, Hysi, PG & Aouizerat, BE 2018, 'A Genome-Wide Association Study Identifies a Candidate Gene Associated With Atazanavir Exposure Measured in Hair', Clinical Pharmacology and Therapeutics, vol. 104, no. 5, pp. 949-956. https://doi.org/10.1002/cpt.1014

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title = "A Genome-Wide Association Study Identifies a Candidate Gene Associated With Atazanavir Exposure Measured in Hair",

abstract = "Hair provides a direct measure of long-term exposure of atazanavir (ATV). We report the results of the first genome-wide association study (GWAS) of ATV exposure measured in hair in an observational cohort representative of US women living with HIV; the Women's Interagency HIV Study. Approximately 14.1 million single nucleotide polymorphisms (SNPs) were analyzed in linear regression-based GWAS, with replication, adjusted for nongenetic predictors collected under conditions of actual use of ATV in 398 participants. Lastly, the PharmGKB database was used to identify pharmacogene associations with ATV exposure. The rs73208473, within intron 1 of SORCS2, resulted in a 0.46-fold decrease in ATV exposure, with the strongest association (P = 1.71×10−8) in GWAS. A priori pharmacogene screening did not identify additional variants statistically significantly associated with ATV exposure, including those previously published in ATV plasma candidate pharmacogene studies. The findings demonstrate the potential value of pharmacogenomic GWAS in ethnically diverse populations under conditions of actual use.",

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AU - Nowicki, Marek J.

AU - Gange, Stephen

AU - Gustafson, Deborah R.

AU - Bacchetti, Peter

AU - Greenblatt, Ruth M.

AU - Hysi, Pirro G.

AU - Aouizerat, Bradley E.

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A Genome-Wide Association Study Identifies a Candidate Gene Associated With Atazanavir Exposure Measured in Hair

Abstract

ASJC Scopus subject areas

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