{
  "abstract": "Almost half of individuals with hypertension fail to achieve recommended blood pressure (BP) goals. Pharmacogenetic gene-drug interactions may alter the efficacy of antihypertensive agents. We conducted a multicenter randomized controlled sub-study of participants (N = 1874) with hypertension and self-reported African ancestry to determine whether pharmacogenetic return of results (RoR) would improve systolic blood pressure (SBP) at 3 months. Participants were randomized to immediate pharmacogenetic RoR (intervention) or delayed RoR at trial completion (control). Clinical decision support conveyed recommendations for YEATS4-guided thiazide diuretic selection and NAT2-guided hydralazine dosing. Prespecified subgroup analyses included those with uncontrolled BP (baseline SBP ≥140 or DBP ≥90 mm Hg) and actionable genotypes. Immediate RoR did not improve SBP at 3 months in a broad population of hypertensive adults with controlled and uncontrolled SBP (covariate-adjusted change in SBP between groups: -0.3 ± 0.74 mm Hg, 95% CI: -1.8, 1.2). In participants with an actionable YEATS4 genotype (N = 867) predicting reduced thiazide efficacy, immediate RoR led to greater SBP reduction at 3 months (-2.46 mm Hg, 95% CI: -4.57 to -0.36). In participants with uncontrolled hypertension at baseline (N = 659), immediate RoR led to a greater reduction in SBP (-2.9 ± 0.74 mm Hg, 95% CI: -5.6, -0.3). Although no SBP reduction was observed in the whole cohort, participants with an actionable YEATS4 genotype or uncontrolled BP who received immediate RoR had a significantly greater SBP improvement than those with delayed RoR. Future studies of antihypertensive pharmacogenetics should recruit individuals with uncontrolled BP and actionable genotypes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy & Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.",
    "Department of Neurology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.",
    "Barbara T. Murphy Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.",
    "Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA.",
    "Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.",
    "Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, University of Florida College of Pharmacy, Gainesville, Florida, USA.",
    "University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA.",
    "The Windreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.",
    "The Hasso Plattner Institute for Digital Health at Mount Sinai, New York, New York, USA.",
    "Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, New York, USA.",
    "Icahn School of Medicine at Mount Sinai, Institute for Health Equity Research, New York, New York, USA.",
    "Bethel Gospel Assembly, New York, New York, USA.",
    "The Institute for Family Health, New York, New York, USA.",
    "Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.",
    "Colleges of Medicine and Pharmacy and Clinical and Translational Science Institute, The Ohio State University, Columbus, Ohio, USA.",
    "Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.",
    "Division of Nephrology & Hypertension, Department of Medicine, Vanderbilt University Medical Center and Geriatric Research Education and Clinical Center (GRECC) and the Veterans' Wellbeing through Innovation, Systems Science and Experience in Learning Health Systems (VETWISE-LHS), Nashville, Tennessee, USA.",
    "Department of Veteran Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.",
    "Department of Medicine, Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA.",
    "Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
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        0
      ],
      "name": "Philip E Empey",
      "orcid": "0000-0001-7474-2339"
    },
    {
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        1
      ],
      "name": "Nita A Limdi",
      "orcid": "0000-0002-4672-8406"
    },
    {
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        2,
        3
      ],
      "name": "Dinushika Mohottige",
      "orcid": "0000-0001-5099-4910"
    },
    {
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        4
      ],
      "name": "Kady-Ann Steen-Burrell",
      "orcid": "0000-0002-8920-8451"
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    {
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        4
      ],
      "name": "Hrishikesh Chakraborty",
      "orcid": "0000-0001-9078-845X"
    },
    {
      "affs": [
        5
      ],
      "name": "Khoa A Nguyen",
      "orcid": "0000-0002-0096-0293"
    },
    {
      "affs": [
        6
      ],
      "name": "Alexander S Parker",
      "orcid": "0000-0001-6820-274X"
    },
    {
      "affs": [
        5
      ],
      "name": "Emily J Cicali",
      "orcid": "0000-0002-3595-9321"
    },
    {
      "affs": [
        2,
        3,
        7,
        8,
        9
      ],
      "name": "Girish N Nadkarni",
      "orcid": "0000-0001-6319-4314"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Michelle A Ramos",
      "orcid": "0000-0002-9975-6275"
    },
    {
      "affs": [
        3,
        10
      ],
      "name": "Sabrina Clermont",
      "orcid": "0000-0001-6990-9069"
    },
    {
      "affs": [
        5
      ],
      "name": "Erica N Elwood",
      "orcid": "0009-0007-7990-5476"
    },
    {
      "affs": [
        11
      ],
      "name": "Mimsie Robinson"
    },
    {
      "affs": [
        12
      ],
      "name": "Nandini Shroff",
      "orcid": "0000-0002-4896-3012"
    },
    {
      "affs": [
        13
      ],
      "name": "Marc B Rosenman"
    },
    {
      "affs": [
        4
      ],
      "name": "Ronald Huang",
      "orcid": "0009-0006-9611-6252"
    },
    {
      "affs": [
        5
      ],
      "name": "Larisa H Cavallari",
      "orcid": "0000-0002-7184-5292"
    },
    {
      "affs": [
        5,
        14
      ],
      "name": "Julie A Johnson",
      "orcid": "0000-0001-9847-1932"
    },
    {
      "affs": [
        15
      ],
      "name": "Paul R Dexter",
      "orcid": "0000-0002-0399-0156"
    },
    {
      "affs": [
        15
      ],
      "name": "Todd C Skaar",
      "orcid": "0000-0002-3849-374X"
    },
    {
      "affs": [
        16,
        17
      ],
      "name": "Kerri L Cavanaugh",
      "orcid": "0000-0002-4031-1714"
    },
    {
      "affs": [
        4,
        18
      ],
      "name": "Christina M Wyatt",
      "orcid": "0000-0002-2900-8140"
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    {
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        3,
        7,
        10,
        19
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      "name": "Carol R Horowitz",
      "orcid": "0000-0003-1517-4700"
    },
    {
      "affs": [
        5
      ],
      "name": "Rhonda M Cooper-DeHoff",
      "orcid": "0000-0002-5198-130X"
    },
    {
      "affs": [
        15
      ],
      "name": "Michael T Eadon",
      "orcid": "0000-0003-3066-2876"
    },
    {
      "name": "IGNITE Pragmatic Trials Network"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7czmh81szt62y.bib",
  "cited_by": 0,
  "doi": "10.1002/cpt.70527",
  "fulltext_url": "https://europepmc.org/articles/PMC13677980",
  "id": "7czmh81szt62y",
  "issns": [
    "0009-9236",
    "1532-6535"
  ],
  "landing_url": "https://europepmc.org/article/MED/42894271",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "3004|Pharmacogenetics and Drug Metabolism"
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  "openalex": "W7222871883",
  "pdf_url": "https://europepmc.org/articles/PMC13677980?pdf=render",
  "pmcid": "PMC13677980",
  "pmid": "42894271",
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7czmh81szt62y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42894271",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894271"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3004|Pharmacogenetics and Drug Metabolism",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "A Pilot Randomized Study of NAT2 and YEATS4 Pharmacogenetic Return of Results in Adults with Hypertension and African Ancestry: The GUARDD-US PGx Study.",
  "title_text": "A Pilot Randomized Study of NAT2 and YEATS4 Pharmacogenetic Return of Results in Adults with Hypertension and African Ancestry: The GUARDD-US PGx Study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/7czmh81szt62y",
  "venue": "Clinical pharmacology and therapeutics",
  "versions": []
}