Abstract P2068: Whole Exome Sequencing And Monogenic Hypertension In A Multiethnic Cohort Of 28,000 Individuals

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2019-09, Vol.74 (Suppl_1)
• Main Authors: Paranjpe, Ishan, Johnson, Kipp, Coca, Steven G, Chan, Lili, He, Cijiang, Murphy, Barbara, Narula, Jagat, Do, Ron, Nadkarni, Girish N
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.74.suppl_1.P2068

Abstract only Hypertension (HTN) is a major cause of morbidity and mortality and a subset may be caused by monogenic mutations. We identified the prevalence of these mutations in a multiethnic cohort and determined their association with blood pressure, appropriate diagnosis, and adverse cardiovascular outcomes. In 27,972 individuals from the Bio Me Biobank (8304 European, 6993 African, 9985 Hispanic, and 2690 Other ancestry), we identified ClinVar mutations pathogenic for secondary hypertension using exome sequencing. 3125 individuals (11.2%) had pathogenic mutations with a majority in genes associated with catecholamine excess ( SDHD , SDHB , TMEM127 , RET ; n=1976) and sodium handling/hyperaldosteronism ( SCNN1G/ CYP11B1 ; n=384). (Fig 1A,B) In a linear model adjusted for sex, age, BMI, and 10 genetic principal components (PCs), individuals with mutations had elevated mean arterial pressure (β=0.7±0.6 mmHg; p=0.03) and increased odds of CAD (adjusted OR=1.12, 95% CI 1.0 to 1.3, p=0.04). Individuals with mutations in sodium handling/hyperaldosteronism genes had increased odds of CHF (adjusted OR = 1.44, 95% CI 1.04 to 1.97; p=0.02) adjusted for age, sex, 10 genetic PCs, and systolic blood pressure. The majority of individuals with mutations were diagnosed with essential HTN (54.2%) and only 7.8% had appropriate diagnoses of secondary HTN or received appropriate biochemical evaluation. (Figure 1C) Individuals with pathogenic mutations had higher blood pressures, elevated risk for CAD/CHF and the majority were not appropriately evaluated or diagnosed. These results suggest exome sequencing may have utility in hypertension diagnosis and management.