{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T03:41:35Z","timestamp":1792381295307,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    Almost half of individuals with hypertension fail to achieve recommended blood pressure (BP) goals. Pharmacogenetic gene\u2010drug interactions may alter the efficacy of antihypertensive agents. We conducted a multicenter randomized controlled sub\u2010study of participants (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20091874) with hypertension and self\u2010reported African ancestry to determine whether pharmacogenetic return of results (RoR) would improve systolic blood pressure (SBP) at 3\u2009months. Participants were randomized to immediate pharmacogenetic RoR (intervention) or delayed RoR at trial completion (control). Clinical decision support conveyed recommendations for\n                    <jats:italic>YEATS4<\/jats:italic>\n                    \u2010guided thiazide diuretic selection and\n                    <jats:italic>NAT2<\/jats:italic>\n                    \u2010guided hydralazine dosing. Prespecified subgroup analyses included those with uncontrolled BP (baseline SBP \u2265140 or DBP \u226590\u2009mm Hg) and actionable genotypes. Immediate RoR did not improve SBP at 3\u2009months in a broad population of hypertensive adults with controlled and uncontrolled SBP (covariate\u2010adjusted change in SBP between groups: \u22120.3\u2009\u00b1\u20090.74\u2009mm Hg, 95% CI: \u22121.8, 1.2). In participants with an actionable\n                    <jats:italic>YEATS4<\/jats:italic>\n                    genotype (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009867) predicting reduced thiazide efficacy, immediate RoR led to greater SBP reduction at 3\u2009months (\u22122.46\u2009mm Hg, 95% CI: \u22124.57 to \u22120.36). In participants with uncontrolled hypertension at baseline (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009659), immediate RoR led to a greater reduction in SBP (\u22122.9\u2009\u00b1\u20090.74\u2009mm Hg, 95% CI: \u22125.6, \u22120.3). Although no SBP reduction was observed in the whole cohort, participants with an actionable\n                    <jats:italic>YEATS4<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70527","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T03:21:44Z","timestamp":1792380104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Pilot Randomized Study of\n                    <scp>NAT2<\/scp>\n                    and\n                    <scp>YEATS4<\/scp>\n                    Pharmacogenetic Return of Results in Adults with Hypertension and African Ancestry: The\n                    <scp>GUARDD<\/scp>\n                    \u2010\n                    <scp>US PGx<\/scp>\n                    Study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-2339","authenticated-orcid":false,"given":"Philip E.","family":"Empey","sequence":"first","affiliation":[{"name":"Department of Pharmacy &amp; Therapeutics University of Pittsburgh School of Pharmacy  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4672-8406","authenticated-orcid":false,"given":"Nita A.","family":"Limdi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heersink School of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5099-4910","authenticated-orcid":false,"given":"Dinushika","family":"Mohottige","sequence":"additional","affiliation":[{"name":"Barbara T. Murphy Division of Nephrology, Department of Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8920-8451","authenticated-orcid":false,"given":"Kady\u2010Ann","family":"Steen\u2010Burrell","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-845X","authenticated-orcid":false,"given":"Hrishikesh","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0096-0293","authenticated-orcid":false,"given":"Khoa A.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6820-274X","authenticated-orcid":false,"given":"Alexander S.","family":"Parker","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine\u2013Jacksonville  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3595-9321","authenticated-orcid":false,"given":"Emily J.","family":"Cicali","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6319-4314","authenticated-orcid":false,"given":"Girish N.","family":"Nadkarni","sequence":"additional","affiliation":[{"name":"Barbara T. Murphy Division of Nephrology, Department of Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"The Windreich Department of Artificial Intelligence and Human Health Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"The Hasso Plattner Institute for Digital Health at Mount Sinai  New York New York USA"},{"name":"Icahn School of Medicine at Mount Sinai The Charles Bronfman Institute for Personalized Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9975-6275","authenticated-orcid":false,"given":"Michelle A.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Icahn School of Medicine at Mount Sinai Institute for Health Equity Research  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6990-9069","authenticated-orcid":false,"given":"Sabrina","family":"Clermont","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Icahn School of Medicine at Mount Sinai Institute for Health Equity Research  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7990-5476","authenticated-orcid":false,"given":"Erica N.","family":"Elwood","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimsie","family":"Robinson","sequence":"additional","affiliation":[{"name":"Bethel Gospel Assembly  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-3012","authenticated-orcid":false,"given":"Nandini","family":"Shroff","sequence":"additional","affiliation":[{"name":"The Institute for Family Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc B.","family":"Rosenman","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9611-6252","authenticated-orcid":false,"given":"Ronald","family":"Huang","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-5292","authenticated-orcid":false,"given":"Larisa H.","family":"Cavallari","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9847-1932","authenticated-orcid":false,"given":"Julie A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy  Gainesville Florida USA"},{"name":"Colleges of Medicine and Pharmacy and Clinical and Translational Science Institute The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-0156","authenticated-orcid":false,"given":"Paul R.","family":"Dexter","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-374X","authenticated-orcid":false,"given":"Todd C.","family":"Skaar","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4031-1714","authenticated-orcid":false,"given":"Kerri L.","family":"Cavanaugh","sequence":"additional","affiliation":[{"name":"Division of Nephrology &amp; 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\u2010LHS)  Nashville Tennessee USA"},{"name":"Department of Veteran Affairs Tennessee Valley Healthcare System  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-8140","authenticated-orcid":false,"given":"Christina M.","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University School of Medicine  Durham North Carolina USA"},{"name":"Department of Medicine, Division of Nephrology Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1517-4700","authenticated-orcid":false,"given":"Carol R.","family":"Horowitz","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"The Windreich Department of Artificial Intelligence and Human Health Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Icahn School of Medicine at Mount Sinai Institute for Health Equity Research  New York New York USA"},{"name":"Department of Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5198-130X","authenticated-orcid":false,"given":"Rhonda M.","family":"Cooper\u2010DeHoff","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-2876","authenticated-orcid":false,"given":"Michael T.","family":"Eadon","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the IGNITE Pragmatic Trials Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_11_1_1","first-page":"1110","article-title":"QuickStats: age\u2010adjusted percentage of adults aged \u226518\u2009years with hypertension, by sex and race and ethnicity","volume":"73","author":"Centers for Disease Control and Prevention (CDC)","year":"2024","journal-title":"MMWR Morb. Mortal. Wkly Rep."},{"key":"e_1_2_11_2_1","unstructured":"Centers for Disease Control and Prevention (CDC).Hypertension Cascade: Hypertension Prevalence Treatment and Control Estimates Among US Adults Aged 18\u2009Years and Older Applying the Criteria From the American College of Cardiology and American Heart Association's 2017 Hypertension Guideline\u2014NHANES 2017\u20132020(2023)."},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/ajh\/hpae141","article-title":"Trends in blood pressure control among US adults with hypertension, 2013\u20132014 to 2021\u20132023","volume":"38","author":"Hardy S.T.","year":"2025","journal-title":"Am. J. Hypertens."},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1161\/HYP.0000000000000066","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA guideline for the prevention, detection, evaluation, and Management of High Blood Pressure in adults: executive summary: a report of the American College of Cardiology\/American Heart Association task force on clinical practice guidelines","volume":"71","author":"Whelton P.K.","year":"2018","journal-title":"Hypertension"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1159\/000510433","article-title":"Genotype\u2010guided hydralazine therapy","volume":"51","author":"Collins K.S.","year":"2020","journal-title":"Am. J. Nephrol."},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/tpj.2012.4","article-title":"Association of chromosome 12 locus with antihypertensive response to hydrochlorothiazide may involve differential YEATS4 expression","volume":"13","author":"Duarte J.D.","year":"2013","journal-title":"Pharmacogenomics J."},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.34067\/KID.0005362021","article-title":"Pharmacogenomics of hypertension in CKD: the CKD\u2010PGX study","volume":"3","author":"Eadon M.T.","year":"2022","journal-title":"Kidney360"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1002\/cpt.70071","article-title":"Clinical Pharmacogenetics implementation consortium guideline for NAT2 genotype and hydralazine therapy","volume":"118","author":"Eadon M.T.","year":"2025","journal-title":"Clin. Pharmacol. Ther."},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"e260528","DOI":"10.1001\/jamanetworkopen.2026.0528","article-title":"Genetic testing for APOL1 in adults with hypertension: the GUARDD\u2010US randomized clinical trial","volume":"9","author":"Eadon M.T.","year":"2026","journal-title":"JAMA Netw. Open"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/cpt.2350","article-title":"An evidence\u2010based framework for evaluating pharmacogenomics knowledge for personalized medicine","volume":"110","author":"Whirl\u2010Carrillo M.","year":"2021","journal-title":"Clin. Pharmacol. 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