Show simple item record

dc.contributor.authorLevy, Danielen_US
dc.contributor.authorLarson, Martin G.en_US
dc.contributor.authorBenjamin, Emelia J.en_US
dc.contributor.authorNewton-Cheh, Christopheren_US
dc.contributor.authorWang, Thomas J.en_US
dc.contributor.authorHwang, Shih-Jenen_US
dc.contributor.authorVasan, Ramachandran S.en_US
dc.contributor.authorMitchell, Gary F.en_US
dc.date.accessioned2011-12-29T21:02:20Z
dc.date.available2011-12-29T21:02:20Z
dc.date.copyright2007
dc.date.issued2007-9-19
dc.identifier.citationLevy, Daniel, Martin G. Larson, Emelia J. Benjamin, Christopher Newton-Cheh, Thomas J. Wang, Shih-Jen Hwang, Ramachandran S. Vasan, Gary F. Mitchell. "Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness" BMC Medical Genetics 8 (Suppl 1): S3. (2007)
dc.identifier.issn1471-2350
dc.identifier.urihttps://hdl.handle.net/2144/2513
dc.description.abstractBACKGROUND: About one quarter of adults are hypertensive and high blood pressure carries increased risk for heart disease, stroke, kidney disease and death. Increased arterial stiffness is a key factor in the pathogenesis of systolic hypertension and cardiovascular disease. Substantial heritability of blood-pressure (BP) and arterial-stiffness suggests important genetic contributions. METHODS: In Framingham Heart Study families, we analyzed genome-wide SNP (Affymetrix 100K GeneChip) associations with systolic (SBP) and diastolic (DBP) BP at a single examination in 1971–1975 (n = 1260), at a recent examination in 1998–2001 (n = 1233), and long-term averaged SBP and DBP from 1971–2001 (n = 1327, mean age 52 years, 54% women) and with arterial stiffness measured by arterial tonometry (carotid-femoral and carotid-brachial pulse wave velocity, forward and reflected pressure wave amplitude, and mean arterial pressure; 1998–2001, n = 644). In primary analyses we used generalized estimating equations in models for an additive genetic effect to test associations between SNPs and phenotypes of interest using multivariable-adjusted residuals. A total of 70,987 autosomal SNPs with minor allele frequency ≥ 0.10, genotype call rate ≥ 0.80, and Hardy-Weinberg equilibrium p ≥ 0.001 were analyzed. We also tested for association of 69 SNPs in six renin-angiotensin-aldosterone pathway genes with BP and arterial stiffness phenotypes as part of a candidate gene search. RESULTS: In the primary analyses, none of the associations attained genome-wide significance. For the six BP phenotypes, seven SNPs yielded p values < 10-5. The lowest p-values for SBP and DBP respectively were rs10493340 (p = 1.7 × 10-6) and rs1963982 (p = 3.3 × 10-6). For the five tonometry phenotypes, five SNPs had p values < 10-5; lowest p-values were for reflected wave (rs6063312, p = 2.1 × 10-6) and carotid-brachial pulse wave velocity (rs770189, p = 2.5 × 10-6) in MEF2C, a regulator of cardiac morphogenesis. We found only weak association of SNPs in the renin-angiotensin-aldosterone pathway with BP or arterial stiffness. CONCLUSION: These results of genome-wide association testing for blood pressure and arterial stiffness phenotypes in an unselected community-based sample of adults may aid in the identification of the genetic basis of hypertension and arterial disease, help identify high risk individuals, and guide novel therapies for hypertension. Additional studies are needed to replicate any associations identified in these analyses.en_US
dc.description.sponsorshipNational Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC 25195); Donald W. Reynold's Foundation; National Institutes of Health (R01-HL70100, R01-HL60040; K24-HL04334); National Insitutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1)en_US
dc.language.isoen
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2007 Levy 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.urihttp://creativecommons.org/licenses/by/2.0
dc.titleFramingham Heart Study 100K Project: Genome-Wide Associations for Blood Pressure and Arterial Stiffnessen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1471-2350-8-S1-S3
dc.identifier.pmid17903302
dc.identifier.pmcid1995621


This item appears in the following Collection(s)

Show simple item record

Copyright 2007 Levy 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.
Except where otherwise noted, this item's license is described as Copyright 2007 Levy 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.