TY - JOUR
T1 - Genome-wide association study of cardiac structure and systolic function in African Americans the Candidate gene Association Resource (CARe) study
AU - Fox, Ervin R.
AU - Musani, Solomon K.
AU - Barbalic, Maja
AU - Lin, Honghuang
AU - Yu, Bing
AU - Ogunyankin, Kofo O.
AU - Smith, Nicholas L.
AU - Kutlar, Abdullah
AU - Glazer, Nicole L.
AU - Post, Wendy S.
AU - Paltoo, Dina N.
AU - Dries, Daniel L.
AU - Farlow, Deborah N.
AU - Duarte, Christine W.
AU - Kardia, Sharon L.
AU - Meyers, Kristin J.
AU - Sun, Yan V.
AU - Arnett, Donna K.
AU - Patki, Amit A.
AU - Sha, Jin
AU - Cui, Xiangqui
AU - Samdarshi, Tandaw E.
AU - Penman, Alan D.
AU - Bibbins-Domingo, Kirsten
AU - Bůžková, Petra
AU - Benjamin, Emelia J.
AU - Bluemke, David A.
AU - Morrison, Alanna C.
AU - Heiss, Gerardo
AU - Carr, J. Jeffrey
AU - Tracy, Russell P.
AU - Mosley, Thomas H.
AU - Taylor, Herman A.
AU - Psaty, Bruce M.
AU - Heckbert, Susan R.
AU - Cappola, Thomas P.
AU - Vasan, Ramachandran S.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Echocardiography
KW - Ethnic
KW - Genome-wide association studies
KW - Left atrium genetics
KW - Left ventricular mass genetics
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U2 - 10.1161/CIRCGENETICS.111.962365
DO - 10.1161/CIRCGENETICS.111.962365
M3 - Review article
C2 - 23275298
AN - SCOPUS:84878038657
SN - 1942-325X
VL - 6
SP - 37
EP - 46
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
IS - 1
ER -