Genome-wide study of resistant hypertension identified from electronic health records

Logan Dumitrescu, Marylyn D. Ritchie, Joshua C. Denny, Nihal M El Rouby, Caitrin W. McDonough, Yuki Bradford, Andrea H. Ramirez, Suzette J Bielinski, Melissa A. Basford, High Seng Chai, Peggy Peissig, David Carrell, Jyotishman Pathak, Luke V. Rasmussen, Xiaoming Wang, Jennifer A. Pacheco, Abel N. Kho, M. Geoffrey Hayes, Martha Matsumoto, Maureen E. SmithRongling Li, Rhonda M. Cooper-DeHoff, Iftikhar Jan Kullo, Christopher G. Chute, Rex L. Chisholm, Gail P. Jarvik, Eric B. Larson, David Carey, Catherine A. McCarty, Marc S. Williams, Dan M. Roden, Erwin Bottinger, Julie A. Johnson, Mariza De Andrade, Dana C. Crawford

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0171745
JournalPLoS One
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

Electronic Health Records
hypertension
electronics
Genes
Blood pressure
Health
Genome
Hypertension
genome
Electronic medical equipment
Antihypertensive Agents
Quality control
Testing
Single Nucleotide Polymorphism
genomics
antihypertensive agents
Genome-Wide Association Study
Genomics
Quality Control
odds ratio

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Dumitrescu, L., Ritchie, M. D., Denny, J. C., Rouby, N. M. E., McDonough, C. W., Bradford, Y., ... Crawford, D. C. (2017). Genome-wide study of resistant hypertension identified from electronic health records. PLoS One, 12(2), [e0171745]. https://doi.org/10.1371/journal.pone.0171745

Genome-wide study of resistant hypertension identified from electronic health records. / Dumitrescu, Logan; Ritchie, Marylyn D.; Denny, Joshua C.; Rouby, Nihal M El; McDonough, Caitrin W.; Bradford, Yuki; Ramirez, Andrea H.; Bielinski, Suzette J; Basford, Melissa A.; Chai, High Seng; Peissig, Peggy; Carrell, David; Pathak, Jyotishman; Rasmussen, Luke V.; Wang, Xiaoming; Pacheco, Jennifer A.; Kho, Abel N.; Hayes, M. Geoffrey; Matsumoto, Martha; Smith, Maureen E.; Li, Rongling; Cooper-DeHoff, Rhonda M.; Kullo, Iftikhar Jan; Chute, Christopher G.; Chisholm, Rex L.; Jarvik, Gail P.; Larson, Eric B.; Carey, David; McCarty, Catherine A.; Williams, Marc S.; Roden, Dan M.; Bottinger, Erwin; Johnson, Julie A.; De Andrade, Mariza; Crawford, Dana C.

In: PLoS One, Vol. 12, No. 2, e0171745, 01.02.2017.

Research output: Contribution to journalArticle

Dumitrescu, L, Ritchie, MD, Denny, JC, Rouby, NME, McDonough, CW, Bradford, Y, Ramirez, AH, Bielinski, SJ, Basford, MA, Chai, HS, Peissig, P, Carrell, D, Pathak, J, Rasmussen, LV, Wang, X, Pacheco, JA, Kho, AN, Hayes, MG, Matsumoto, M, Smith, ME, Li, R, Cooper-DeHoff, RM, Kullo, IJ, Chute, CG, Chisholm, RL, Jarvik, GP, Larson, EB, Carey, D, McCarty, CA, Williams, MS, Roden, DM, Bottinger, E, Johnson, JA, De Andrade, M & Crawford, DC 2017, 'Genome-wide study of resistant hypertension identified from electronic health records', PLoS One, vol. 12, no. 2, e0171745. https://doi.org/10.1371/journal.pone.0171745
Dumitrescu L, Ritchie MD, Denny JC, Rouby NME, McDonough CW, Bradford Y et al. Genome-wide study of resistant hypertension identified from electronic health records. PLoS One. 2017 Feb 1;12(2). e0171745. https://doi.org/10.1371/journal.pone.0171745
Dumitrescu, Logan ; Ritchie, Marylyn D. ; Denny, Joshua C. ; Rouby, Nihal M El ; McDonough, Caitrin W. ; Bradford, Yuki ; Ramirez, Andrea H. ; Bielinski, Suzette J ; Basford, Melissa A. ; Chai, High Seng ; Peissig, Peggy ; Carrell, David ; Pathak, Jyotishman ; Rasmussen, Luke V. ; Wang, Xiaoming ; Pacheco, Jennifer A. ; Kho, Abel N. ; Hayes, M. Geoffrey ; Matsumoto, Martha ; Smith, Maureen E. ; Li, Rongling ; Cooper-DeHoff, Rhonda M. ; Kullo, Iftikhar Jan ; Chute, Christopher G. ; Chisholm, Rex L. ; Jarvik, Gail P. ; Larson, Eric B. ; Carey, David ; McCarty, Catherine A. ; Williams, Marc S. ; Roden, Dan M. ; Bottinger, Erwin ; Johnson, Julie A. ; De Andrade, Mariza ; Crawford, Dana C. / Genome-wide study of resistant hypertension identified from electronic health records. In: PLoS One. 2017 ; Vol. 12, No. 2.
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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.",
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AU - Bradford, Yuki

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AU - Bielinski, Suzette J

AU - Basford, Melissa A.

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AU - Peissig, Peggy

AU - Carrell, David

AU - Pathak, Jyotishman

AU - Rasmussen, Luke V.

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AU - Pacheco, Jennifer A.

AU - Kho, Abel N.

AU - Hayes, M. Geoffrey

AU - Matsumoto, Martha

AU - Smith, Maureen E.

AU - Li, Rongling

AU - Cooper-DeHoff, Rhonda M.

AU - Kullo, Iftikhar Jan

AU - Chute, Christopher G.

AU - Chisholm, Rex L.

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AU - Carey, David

AU - McCarty, Catherine A.

AU - Williams, Marc S.

AU - Roden, Dan M.

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