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.
Bibliographical noteFunding Information:
The eMERGE Network is funded by NHGRI, with additional funding from NIGMS through the following grants: U01HG04599 and U01HG006379 to Mayo Clinic; U01HG004610 and U01HG006375 to Group Health Cooperative and University of Washington, Seattle; U01HG004608 to Marshfield Clinic; U01HG006389 to Essentia Institute of Rural Health; U01HG004609 and U01HG006388 to Northwestern University; U01HG04603 and U01HG006378 to Vanderbilt University; U01HG006385 to the Coordinating Center; U01HG006382 to Geisinger Clinic; U01HG006380 to Mount Sinai School of Medicine; U01HG006830 to The Children's Hospital of Philadelphia; and U01HG006828 to Cincinnati Children's Hospital and Boston Children's Hospital. A portion of the dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center's BioVU, supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH, and the Mayo Clinic Biobank supported by the Mayo Clinic Center for Individualized Medicine. INVEST-GENES was funded by NIH grants R01 HL074730 and U01 GM074492. SPS3 and SPS3-GENES were funded by NIH grants U01 NS038529, U01 GM074492, and R01 NS073346. CWM was also supported by KL2 TR001429. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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