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

Dumitrescu L1, Ritchie MD2, Denny JC3,4, El Rouby NM5, McDonough CW5, Bradford Y2, Ramirez AH4, Bielinski SJ6, Basford MA7, Chai HS8, Peissig P9, Carrell D10, Pathak J8, Rasmussen LV11, Wang X3, Pacheco JA12, Kho AN13, Hayes MG13, Matsumoto M8, Smith ME12, Li R14, Cooper-DeHoff RM5,15, Kullo IJ16, Chute CG17, Chisholm RL12, Jarvik GP18, Larson EB10, Carey D19, McCarty CA20, Williams MS21, Roden DM4,22, Bottinger E23, Johnson JA5,24, de Andrade M8, Crawford DC15.

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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.

PMID:: 28222112
PMCID:: PMC5319785
DOI:: 10.1371/journal.pone.0171745

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