Document Detail


Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) study.
MedLine Citation:
PMID:  23275298     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: 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.
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, 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.
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.
Authors:
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 Sha; Xiangqui 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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-28
Journal Detail:
Title:  Circulation. Cardiovascular genetics     Volume:  6     ISSN:  1942-3268     ISO Abbreviation:  Circ Cardiovasc Genet     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2013-08-19     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  101489144     Medline TA:  Circ Cardiovasc Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37-46     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
African Americans / genetics*
Aged
Cohort Studies
Diastole
Echocardiography
European Continental Ancestry Group / genetics
Female
Genome-Wide Association Study*
Genotype
Heart / anatomy & histology,  physiology*
Humans
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide*
Systole*
Grant Support
ID/Acronym/Agency:
HL 087652/HL/NHLBI NIH HHS; HL 100245/HL/NHLBI NIH HHS; N01 HC025195/HC/NHLBI NIH HHS; N01 HC065226/HC/NHLBI NIH HHS; N01 HC095170/HC/NHLBI NIH HHS; N01 HC095171/HC/NHLBI NIH HHS; N01 HC095172/HC/NHLBI NIH HHS; P60 MD002249/MD/NIMHD NIH HHS; R01 AG028321/AG/NIA NIH HHS; R01 DK077950-03/DK/NIDDK NIH HHS; R01 HD067264/HD/NICHD NIH HHS; R01 HL088577/HL/NHLBI NIH HHS; R01 HL09257/HL/NHLBI NIH HHS; R01 HL102214/HL/NHLBI NIH HHS; R01HL101161-01-A1/HL/NHLBI NIH HHS; RC1 HD101056/HD/NICHD NIH HHS; RC1 HL100185/HL/NHLBI NIH HHS; RC4 AG039029/AG/NIA NIH HHS
Comments/Corrections

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