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Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) study.
Monday,2015-03-09 16:30 America/Los_Angeles — zdrager
| Title | Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) study. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Fox, ER, Musani, SK, Barbalic, M, Lin, H, Yu, B, Ogunyankin, KO, Smith, NL, Kutlar, A, Glazer, NL, Post, WS, Paltoo, DN, Dries, DL, Farlow, DN, Duarte, CW, Kardia, SL, Meyers, KJ, Sun, YV, Arnett, DK, Patki, AA, Sha, J, Cui, X, Samdarshi, TE, Penman, AD, Bibbins-Domingo, K, Bůzková, P, Benjamin, EJ, Bluemke, DA, Morrison, AC, Heiss, G, J Carr, J, Tracy, RP, Mosley, TH, Taylor, HA, Psaty, BM, Heckbert, SR, Cappola, TP, Vasan, RS |
| Journal | Circ Cardiovasc Genet |
| Volume | 6 |
| Issue | 1 |
| Pagination | 37-46 |
| Date Published | 2013 Feb |
| ISSN | 1942-3268 |
| Keywords | African Americans, Aged, Cohort Studies, Diastole, Echocardiography, European Continental Ancestry Group, Female, Genome-Wide Association Study, Genotype, Heart, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Systole |
| Abstract | <p><b>BACKGROUND: </b>Using data from 4 community-based cohorts of African Americans, we tested the association between genome-wide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study.</p><p><b>METHODS AND RESULTS: </b>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, genome-wide 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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1161/CIRCGENETICS.111.962365 |
| Alternate Journal | Circ Cardiovasc Genet |
| PubMed ID | 23275298 |
| PubMed Central ID | PMC3591479 |
| Grant List | HL 087652 / HL / NHLBI NIH HHS / United States HL 100245 / HL / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States N01 HC065226 / HC / NHLBI NIH HHS / United States N01 HC095170 / HC / NHLBI NIH HHS / United States N01 HC095171 / HC / NHLBI NIH HHS / United States N01 HC095172 / HC / NHLBI NIH HHS / United States P60 MD002249 / MD / NIMHD NIH HHS / United States P60 MD002249 / MD / NIMHD NIH HHS / United States R01 AG028321 / AG / NIA NIH HHS / United States R01 DK077950-03 / DK / NIDDK NIH HHS / United States R01 HD067264 / HD / NICHD NIH HHS / United States R01 HL088577 / HL / NHLBI NIH HHS / United States R01 HL09257 / HL / NHLBI NIH HHS / United States R01 HL101161 / HL / NHLBI NIH HHS / United States R01 HL102214 / HL / NHLBI NIH HHS / United States R01HL101161-01-A1 / HL / NHLBI NIH HHS / United States RC1 HD101056 / HD / NICHD NIH HHS / United States RC1 HL100185 / HL / NHLBI NIH HHS / United States RC4 AG039029 / AG / NIA NIH HHS / United States |