Genome-Wide Association of Echocardiographic Dimensions, Brachial Artery Endothelial Function and Treadmill Exercise Responses in the Framingham Heart Study

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dc.contributor.author Vasan, Ramachandran S en_US
dc.contributor.author Larson, Martin G en_US
dc.contributor.author Aragam, Jayashri en_US
dc.contributor.author Wang, Thomas J en_US
dc.contributor.author Mitchell, Gary F en_US
dc.contributor.author Kathiresan, Sekar en_US
dc.contributor.author Newton-Cheh, Christopher en_US
dc.contributor.author Vita, Joseph A en_US
dc.contributor.author Keyes, Michelle J en_US
dc.contributor.author O'Donnell, Christopher J en_US
dc.contributor.author Levy, Daniel en_US
dc.contributor.author Benjamin, Emelia J en_US
dc.date.accessioned 2011-12-29T21:02:20Z
dc.date.available 2011-12-29T21:02:20Z
dc.date.copyright 2007 en_US
dc.date.issued 2007-9-19 en_US
dc.identifier.citation Vasan, Ramachandran S, Martin G Larson, Jayashri Aragam, Thomas J Wang, Gary F Mitchell, Sekar Kathiresan, Christopher Newton-Cheh, Joseph A Vita, Michelle J Keyes, Christopher J O'Donnell, Daniel Levy, Emelia J Benjamin. "Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study" BMC Medical Genetics 8 (Suppl 1): S2. (2007) en_US
dc.identifier.issn 1471-2350 en_US
dc.identifier.uri http://hdl.handle.net/2144/2510
dc.description.abstract BACKGROUND: Echocardiographic left ventricular (LV) measurements, exercise responses to standardized treadmill test (ETT) and brachial artery (BA) vascular function are heritable traits that are associated with cardiovascular disease risk. We conducted a genome-wide association study (GWAS) in the community-based Framingham Heart Study. METHODS: We estimated multivariable-adjusted residuals for quantitative echocardiography, ETT and BA function traits. Echocardiography residuals were averaged across 4 examinations and included LV mass, diastolic and systolic dimensions, wall thickness, fractional shortening, left atrial and aortic root size. ETT measures (single exam) included systolic blood pressure and heart rate responses during exercise stage 2, and at 3 minutes post-exercise. BA measures (single exam) included vessel diameter, flow-mediated dilation (FMD), and baseline and hyperemic flow responses. Generalized estimating equations (GEE), family-based association tests (FBAT) and variance-components linkage were used to relate multivariable-adjusted trait residuals to 70,987 SNPs (Human 100K GeneChip, Affymetrix) restricted to autosomal SNPs with minor allele frequency ≥0.10, genotype call rate ≥0.80, and Hardy-Weinberg equilibrium p ≥ 0.001. RESULTS: We summarize results from 17 traits in up to 1238 related middle-aged to elderly men and women. Results of all association and linkage analyses are web-posted at . We confirmed modest-to-strong heritabilities (estimates 0.30–0.52) for several Echo, ETT and BA function traits. Overall, p < 10-5 in either GEE or FBAT models were observed for 21 SNPs (nine for echocardiography, eleven for ETT and one for BA function). The top SNPs associated were (GEE results): LV diastolic dimension, rs1379659 (SLIT2, p = 1.17*10-7); LV systolic dimension, rs10504543 (KCNB2, p = 5.18*10-6); LV mass, rs10498091 (p = 5.68*10-6); Left atrial size, rs1935881 (FAM5C, p = 6.56*10-6); exercise heart rate, rs6847149 (NOLA1, p = 2.74*10-6); exercise systolic blood pressure, rs2553268 (WRN, p = 6.3*10-6); BA baseline flow, rs3814219 (OBFC1, 9.48*10-7), and FMD, rs4148686 (CFTR, p = 1.13*10-5). Several SNPs are reasonable biological candidates, with some being related to multiple traits suggesting pleiotropy. The peak LOD score was for LV mass (4.38; chromosome 5); the 1.5 LOD support interval included NRG2. CONCLUSION: In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community. en_US
dc.description.sponsorship National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1); National Institutes of Health (K23-HL-074077, K23-HL080025, 6R01-NS 17950, 1R01 HL 60040, RO1 HL70100, HL080124, K24-HL04334) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2007 Vasan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title Genome-Wide Association of Echocardiographic Dimensions, Brachial Artery Endothelial Function and Treadmill Exercise Responses in the Framingham Heart Study en_US
dc.type article en_US
dc.identifier.doi 10.1186/1471-2350-8-S1-S2 en_US
dc.identifier.pubmedid 17903301 en_US
dc.identifier.pmcid 1995617 en_US

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