The role of rare variants in systolic blood pressure: Analysis of exomechip data in HyperGEN African Americans

Yun Ju Sung, Jacob Basson, Nuo Cheng, Khanh Dung H. Nguyen, Priyanka Nandakumar, Steven Hunt, Donna K. Arnett, Victor G. Dávila-Román, Dabeeru C. Rao, Aravinda Chakravarti

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3 Citations (Scopus)

Abstract

Cardiovascular diseases are among the most significant health problems in the United States today, with their major risk factor, hypertension, disproportionately affecting African Americans (AAs). Although GWAS have identified dozens of common variants associated with blood pressure (BP) and hypertension in European Americans, these variants collectively explain <2.5% of BP variance, and most of the genetic variants remain yet to be identified. Here, we report the results from rare-variant analysis of systolic BP using 94,595 rare and low-frequency variants (minor allele frequency, MAF, <5%) from the Illumina exome array genotyped in 2,045 HyperGEN AAs. In addition to single-variant analysis, 4 gene-level association tests were used for analysis: burden and family-based SKAT tests using MAF cutoffs of 1 and 5%. The gene-based methods often provided lower p values than the single-variant approach. Some consistency was observed across these 4 gene-based analysis options. While neither the gene-based analyses nor the single-variant analysis produced genome-wide significant results, the top signals, which had supporting evidence from multiple gene-based methods, were of borderline significance. Though additional molecular validations are required, 6 of the 16 most promising genes are biologically plausible with physiological connections to BP regulation.

Original languageEnglish
Pages (from-to)20-27
Number of pages8
JournalHuman Heredity
Volume79
Issue number1
DOIs
Publication statusPublished - 6 Apr 2015
Externally publishedYes

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Keywords

  • Burden tests
  • ExomeChip
  • Family studies
  • Gene-based analysis
  • Rare variants
  • SKAT
  • Systolic blood pressure

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics
  • Genetics(clinical)

Cite this

Sung, Y. J., Basson, J., Cheng, N., Nguyen, K. D. H., Nandakumar, P., Hunt, S., Arnett, D. K., Dávila-Román, V. G., Rao, D. C., & Chakravarti, A. (2015). The role of rare variants in systolic blood pressure: Analysis of exomechip data in HyperGEN African Americans. Human Heredity, 79(1), 20-27. https://doi.org/10.1159/000375373