Rare coding variants associated with blood pressure variation in 15 914 individuals of African ancestry

Priyanka Nandakumar, Dongwon Lee, Melissa A. Richard, Fasil Tekola-Ayele, Bamidele O. Tayo, Erin Ware, Yun J. Sung, Babatunde Salako, Adesola Ogunniyi, C. Charles Gu, Megan L. Grove, Myriam Fornage, Sharon Kardia, Charles Rotimi, Richard S. Cooper, Alanna C. Morrison, Georg Ehret, Aravinda Chakravarti

Research output: Contribution to journalArticle

Abstract

Objectives: Hypertension is a major risk factor for all cardiovascular diseases, especially among African Americans. This study focuses on identifying specific blood pressure (BP) genes using 15 914 individuals of African ancestry from eight cohorts (Africa America Diabetes Mellitus, Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in young Adults, Genetics Network, Genetic Epidemiology Network of Arteriopathy, Howard University Family Study, Hypertension Genetic Epidemiology Network, and Loyola University Chicago Cohort) to further genetic findings in this population which has generally been underrepresented in BP studies. Methods: We genotyped and performed various single variant and gene-based exome-wide analyses on 15 914 individuals on the Illumina HumanExome Beadchip v1.0 or v1.1 to test association with SBP and DBP long-term average residuals that were adjusted for age, age-squared, sex, and BMI. Results: We identified rare variants affecting SBP and DBP in 10 genes: AFF1, GAPDHS, SLC28A3, COL6A1, CRYBA2, KRBA1, SEL1L3, YOD1, CCDC13, and QSOX1. Prior experimental evidence for six of these 10 candidate genes supports their involvement in cardiovascular mechanisms, corroborating their potential roles in BP regulation. Conclusion: Although our results require replication or validation due to their low numbers of carriers, and an ethnicity-specific genotyping array may be more informative, this study, which has identified several candidate genes in this population most susceptible to hypertension, presents one of the largest African-ancestry BP studies to date and the largest including analysis of rare variants.

Original languageEnglish (US)
Pages (from-to)1381-1389
Number of pages9
JournalJournal of hypertension
Volume35
Issue number7
DOIs
StatePublished - Jul 1 2017

Keywords

  • African Americans
  • blood pressure
  • epidemiologic studies
  • exome
  • genome-wide association study
  • hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Nandakumar, P., Lee, D., Richard, M. A., Tekola-Ayele, F., Tayo, B. O., Ware, E., Sung, Y. J., Salako, B., Ogunniyi, A., Gu, C. C., Grove, M. L., Fornage, M., Kardia, S., Rotimi, C., Cooper, R. S., Morrison, A. C., Ehret, G., & Chakravarti, A. (2017). Rare coding variants associated with blood pressure variation in 15 914 individuals of African ancestry. Journal of hypertension, 35(7), 1381-1389. https://doi.org/10.1097/HJH.0000000000001319