title: Pharmacogenomic Genome-Wide Meta-Analysis of Blood Pressure Response to β-Blockers in Hypertensive African Americans.
abstract: African Americans suffer a higher prevalence of hypertension compared with other racial/ethnic groups. In this study, we performed a pharmacogenomic genome-wide association study of blood pressure (BP) response to β-blockers in African Americans with uncomplicated hypertension. Genome-wide meta-analysis was performed in 318 African American hypertensive participants in the 2 Pharmacogenomic Evaluation of Antihypertensive Responses studies: 150 treated with atenolol monotherapy and 168 treated with metoprolol monotherapy. The analysis adjusted for age, sex, baseline BP and principal components for ancestry. Genome-wide significant variants with P<5×10(-8) and suggestive variants with P<5×10(-7) were evaluated in an additional cohort of 141 African Americans treated with the addition of atenolol to hydrochlorothiazide treatment. The validated variants were then meta-analyzed in these 3 groups of African Americans. Two variants discovered in the monotherapy meta-analysis were validated in the add-on therapy. African American participants heterozygous for SLC25A31 rs201279313 deletion versus wild-type genotype had better diastolic BP response to atenolol monotherapy, metoprolol monotherapy, and atenolol add-on therapy: -9.3 versus -4.6, -9.6 versus -4.8, and -9.7 versus -6.4 mm Hg, respectively (3-group meta-analysis P=2.5×10(-8), β=-4.42 mm Hg per variant allele). Similarly, LRRC15 rs11313667 was validated for systolic BP response to β-blocker therapy with 3-group meta-analysis P=7.2×10(-8) and β=-3.65 mm Hg per variant allele. In this first pharmacogenomic genome-wide meta-analysis of BP response to β-blockers in African Americans, we identified novel variants that may provide valuable information for personalized antihypertensive treatment in this group.
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.). gong@cop.ufl.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Wang
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Amber L
authors.initials: AL
authors.lastname: Beitelshees
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Caitrin W
authors.initials: CW
authors.lastname: McDonough
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Karen
authors.initials: K
authors.lastname: Hall
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Siegfried O F
authors.initials: SO
authors.lastname: Schmidt
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Robert W
authors.initials: RW
authors.lastname: Curry
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: John G
authors.initials: JG
authors.lastname: Gums
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Arlene B
authors.initials: AB
authors.lastname: Chapman
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.affiliation: From the Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (Y.G., C.W.M., T.Y.L., J.G.G., R.M.C.-D., J.A.J.), Department of Community Health and Family Medicine, College of Medicine (K.H., S.O.F.S., R.W.C., J.G.G.), and Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), University of Florida, Gainesville; Department of Epidemiology, Human Genetics & Environmental Sciences, Center for Human Genetics, University of Texas Health Science Center at Houston (Z.W., E.B.); Department of Medicine and Program in Personalized & Genomic Medicine, University of Maryland, Baltimore (A.L.B.); Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (K.R.B.) and Division of Nephrology and Hypertension (S.T.T.), Mayo Clinic, Rochester, MN; and Department of Medicine, University of Chicago, IL. (A.B.C.).
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D001741:Black or African American; D001794:Blood Pressure / Q000502:physiology*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000208:ethnology / Q000503:physiopathology; D009017:Morbidity / Q000639:trends; D010597:Pharmacogenetics / Q000379:methods*; D014481:United States / Q000453:epidemiology
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: African Americans; GWAS; PEAR; blood pressure response; pharmacogenomics; β-blockers