@article{4053e61c97f94070bd6fd8e75ae72ab8,
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.",
author = "Bani Tamraz and Yong Huang and French, {Audrey L.} and Seble Kassaye and Kathryn Anastos and Nowicki, {Marek J.} and Stephen Gange and Gustafson, {Deborah R.} and Peter Bacchetti and Greenblatt, {Ruth M.} and Hysi, {Pirro G.} and Aouizerat, {Bradley E.}",
note = "Funding Information: UCSF-Gladstone Center For AIDS Research Grant: Bani Tamraz P30 A1027763; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Kathryn Anastos U01-AI-035004; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Deborah (R) Gustafson U01-AI-031834; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Audrey (L) French U01-AI-034993; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Seble Kassaye U01-AI-034994; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Ruth (M.) Greenblatt, Bradley (E) Aouizerat U01-AI-034989; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Stephen (J.) Gange U01-AI-042590; HHS | NIH | National Institute of Child Health and Human Development (NICHD): Marek (J) Nowicki U01-HD-032632; UCSF CTSA: Peter Bacchetti UL1-TR000004. Funding Information: UCSF-Gladstone Center For AIDS Research Grant: Bani Tamraz P30 A1027763; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Kathryn Anastos U01-AI-035004; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Deborah (R) Gustafson U01-AI-031834; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Audrey (L) French U01-AI-034993; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Seble Kassaye U01-AI-034994; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Ruth (M.) Greenblatt, Bradley (E) Aouizerat U01-AI-034989; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): Stephen (J.) Gange U01-AI-042590; HHS | NIH | National Institute of Child Health and Human Development (NICHD): Marek (J) Nowicki U01-HD-032632; UCSF CTSA: Peter Bacchetti UL1-TR000004. Data in this study were collected by the Women's Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I ? WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the NIH Office of Research on Women's Health. WIHS data collection and statistical analysis is also supported by UL1-TR000004 (UCSF CTSA) and data collection by UL1-TR000454 (Atlanta CTSA). Bani Tamraz was also supported by UCSF-Gladstone Center For AIDS Research grant (P30 A1027763). Funding Information: and data collection by UL1-TR000454 (Atlanta CTSA). Bani Tamraz was also supported by UCSF-Gladstone Center For AIDS Research grant (P30 A1027763). Funding Information: Data in this study were collected by the Women{\textquoteright}s Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Connie Wofsy Women{\textquoteright}s HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I – WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the NIH Office of Research on Women{\textquoteright}s Health. WIHS data collection and statistical analysis is also supported by UL1-TR000004 (UCSF CTSA) Publisher Copyright: {\textcopyright} 2018 The American Society for Clinical Pharmacology and Therapeutics",
year = "2018",
month = nov,
doi = "10.1002/cpt.1014",
language = "English (US)",
volume = "104",
pages = "949--956",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "5",
}
