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Abstract: SA-PO312

Whole-Exome Sequencing and Monogenic Hypertension in a Multiethnic Cohort

Session Information

Category: Hypertension and CVD

  • 1401 Hypertension and CVD: Epidemiology, Risk Factors, and Prevention

Authors

  • Paranjpe, Ishan, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Johnson, Kipp W., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Chan, Lili, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • He, John Cijiang, Mount Sinai School of Medicine, New York, New York, United States
  • Murphy, Barbara T., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Do, Ron, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Nadkarni, Girish N., Ichan School of Medicine, New York, New York, United States
Background

A subset of hypertension (HTN) 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.

Methods

In 27,972 individuals from the BioMe Biobank (8304 European, 6993 African, 9985 Hispanic, and 2690 Other ancestry), we identified ClinVar mutations pathogenic for secondary hypertension using exome sequencing. We conducted association analyses with mean arterial pressure and coronary artery disease (CAD)/congestive heart failure (CHF) and assessed whether individuals with mutations had appropriate diagnosis/evaluation.

Results

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). Individuals with mutations had elevated mean arterial pressure (b=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) adjusting for sex, age, BMI, and 10 genetic principal components (PCs). Individuals with mutations in sodium handling/hyperaldosteronism genes had increased CHF (adjusted OR = 1.44, 95% CI 1.04 to 1.9; p=0.02) adjusted for age, sex, 10 PCs, and 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)

Conclusion

Individuals with pathogenic mutations had higher blood pressures and elevated risk for CAD/CHF. The majority were not appropriately evaluated/diagnosed. These results suggest exome sequencing may have utility in hypertension diagnosis and management.

Funding

  • NIDDK Support