Genome-wide association study of cardiac structure and systolic function in African Americans the Candidate gene Association Resource (CARe) study

Ervin R. Fox, Solomon K. Musani, Maja Barbalic, Honghuang Lin, Bing Yu, Kofo O. Ogunyankin, Nicholas L. Smith, Abdullah Kutlar, Nicole L. Glazer, Wendy S. Post, Dina N. Paltoo, Daniel L. Dries, Deborah N. Farlow, Christine W. Duarte, Sharon L. Kardia, Kristin J. Meyers, Yan V. Sun, Donna K. Arnett, Amit A. Patki, Jin ShaXiangqui Cui, Tandaw E. Samdarshi, Alan D. Penman, Kirsten Bibbins-Domingo, Petra Bůžková, Emelia J. Benjamin, David A. Bluemke, Alanna C. Morrison, Gerardo Heiss, J. Jeffrey Carr, Russell P. Tracy, Thomas H. Mosley, Herman A. Taylor, Bruce M. Psaty, Susan R. Heckbert, Thomas P. Cappola, Ramachandran S. Vasan

Research output: Contribution to journalReview article

28 Scopus citations

Abstract

Background-Using data from 4 community-based cohorts of African Americans, we tested the association between genomewide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study. Methods and Results-Among 6765 African Americans, we related age, sex, height, and weight-adjusted residuals for 9 cardiac phenotypes (assessed by echocardiogram or magnetic resonance imaging) to 2.5 million single-nucleotide polymorphisms genotyped using Genome-wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within the cohort, genomewide association analysis was conducted, followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0 ×10-7). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested lookups in 1 consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (P=1.43×10-7) for left ventricular mass, rs7213314 in WIPI1 (P=1.68×10-7) for left ventricular internal diastolic diameter, rs1571099 in PPAPDC1A (P=2.57×10-8) for interventricular septal wall thickness, and rs9530176 in KLF5 (P=4.02×10-7) for ejection fraction. Associated variants were enriched in 3 signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry was confirmed in lookups in EchoGEN. Conclusions-In the largest genome-wide association study of cardiac structure and function to date in African Americans, we identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance. Replication results suggest that these loci may be unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalCirculation: Cardiovascular Genetics
Volume6
Issue number1
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Keywords

  • Echocardiography
  • Ethnic
  • Genome-wide association studies
  • Left atrium genetics
  • Left ventricular mass genetics

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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    Fox, E. R., Musani, S. K., Barbalic, M., Lin, H., Yu, B., Ogunyankin, K. O., Smith, N. L., Kutlar, A., Glazer, N. L., Post, W. S., Paltoo, D. N., Dries, D. L., Farlow, D. N., Duarte, C. W., Kardia, S. L., Meyers, K. J., Sun, Y. V., Arnett, D. K., Patki, A. A., ... Vasan, R. S. (2013). Genome-wide association study of cardiac structure and systolic function in African Americans the Candidate gene Association Resource (CARe) study. Circulation: Cardiovascular Genetics, 6(1), 37-46. https://doi.org/10.1161/CIRCGENETICS.111.962365