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


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


Genome-Wide Association of Echocardiographic Dimensions, Brachial Artery Endothelial Function and Treadmill Exercise Responses in the Framingham Heart Study - Download this document for free, or read online. Document in PDF available to download.

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

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.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.

MED: Medicine Papers - Whitaker Cardiovascular Institute Papers - CAS: Mathematics: Scholarly Papers - Framingham Heart Study Papers -



Author: Vasan, Ramachandran S. - Larson, Martin G. - Aragam, Jayashri - Wang, Thomas J. - Mitchell, Gary F. - Kathiresan, Sekar - Newton-

Source: https://open.bu.edu/







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