title: Genome-wide study of resistant hypertension identified from electronic health records.
abstract: Resistant hypertension is defined as high blood pressure that remains above treatment goals in spite of the concurrent use of three antihypertensive agents from different classes. Despite the important health consequences of resistant hypertension, few studies of resistant hypertension have been conducted. To perform a genome-wide association study for resistant hypertension, we defined and identified cases of resistant hypertension and hypertensives with treated, controlled hypertension among >47,500 adults residing in the US linked to electronic health records (EHRs) and genotyped as part of the electronic MEdical Records & GEnomics (eMERGE) Network. Electronic selection logic using billing codes, laboratory values, text queries, and medication records was used to identify resistant hypertension cases and controls at each site, and a total of 3,006 cases of resistant hypertension and 876 controlled hypertensives were identified among eMERGE Phase I and II sites. After imputation and quality control, a total of 2,530,150 SNPs were tested for an association among 2,830 multi-ethnic cases of resistant hypertension and 876 controlled hypertensives. No test of association was genome-wide significant in the full dataset or in the dataset limited to European American cases (n = 1,719) and controls (n = 708). The most significant finding was CLNK rs13144136 at p = 1.00x10-6 (odds ratio = 0.68; 95% CI = 0.58-0.80) in the full dataset with similar results in the European American only dataset. We also examined whether SNPs known to influence blood pressure or hypertension also influenced resistant hypertension. None was significant after correction for multiple testing. These data highlight both the difficulties and the potential utility of EHR-linked genomic data to study clinically-relevant traits such as resistant hypertension.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Logan
authors.initials: L
authors.lastname: Dumitrescu
authors.affiliation: Biomedical and Translational Informatics, Geisinger Health System, Danville, Pennsylvania, United States of America.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, United States of America.|Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Nihal M
authors.initials: NM
authors.lastname: El Rouby
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Caitrin W
authors.initials: CW
authors.lastname: McDonough
authors.affiliation: Biomedical and Translational Informatics, Geisinger Health System, Danville, Pennsylvania, United States of America.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Bradford
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Ramirez
authors.affiliation: Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Suzette J
authors.initials: SJ
authors.lastname: Bielinski
authors.affiliation: Office of Research, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Basford
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: High Seng
authors.initials: HS
authors.lastname: Chai
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, United States of America.
authors.forename: Peggy
authors.initials: P
authors.lastname: Peissig
authors.affiliation: Group Health Research Institute, Seattle, Washington, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Carrell
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Jyotishman
authors.initials: J
authors.lastname: Pathak
authors.affiliation: Department of Preventive Medicine, Division of Health and Biomedical Informatics, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Luke V
authors.initials: LV
authors.lastname: Rasmussen
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Genetic Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Pacheco
authors.affiliation: Department Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Abel N
authors.initials: AN
authors.lastname: Kho
authors.affiliation: Department Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Martha
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Center for Genetic Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Smith
authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, Maryland, United States of America.
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.|Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.affiliation: Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
authors.affiliation: Division of General Internal Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Chute
authors.affiliation: Center for Genetic Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Rex L
authors.initials: RL
authors.lastname: Chisholm
authors.affiliation: Department of Medicine, University of Washington Medical Center, Seattle, Washington, United States of America.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.affiliation: Group Health Research Institute, Seattle, Washington, United States of America.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.affiliation: Weis Center for Research, Geisinger Health System, Danville, Pennsylvania, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Carey
authors.affiliation: Essentia Institute of Rural Health, Duluth, Minnesota, United States of America.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.affiliation: Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania, United States of America.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Williams
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.|Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Charles R. Bronfman Institute for Personalized Medicine, Mount Sinai, New York, New York, United States of America.
authors.forename: Erwin
authors.initials: E
authors.lastname: Bottinger
authors.affiliation: Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.|Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.affiliation: Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000235:genetics; D016022:Case-Control Studies; D003195:Computer Communication Networks; D066264:Datasets as Topic; D004351:Drug Resistance / Q000235:genetics*; D057286:Electronic Health Records; D005006:Ethnicity / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D000959:Antihypertensive Agents