Document Detail


Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness.
MedLine Citation:
PMID:  17903302     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: 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 > or = 0.10, genotype call rate > or = 0.80, and Hardy-Weinberg equilibrium p > or = 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 x 10(-6)) and rs1963982 (p = 3.3 x 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 x 10(-6)) and carotid-brachial pulse wave velocity (rs770189, p = 2.5 x 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.
Authors:
Daniel Levy; Martin G Larson; Emelia J Benjamin; Christopher Newton-Cheh; Thomas J Wang; Shih-Jen Hwang; Ramachandran S Vasan; Gary F Mitchell
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-09-19
Journal Detail:
Title:  BMC medical genetics     Volume:  8 Suppl 1     ISSN:  1471-2350     ISO Abbreviation:  BMC Med. Genet.     Publication Date:  2007  
Date Detail:
Created Date:  2007-10-01     Completed Date:  2007-11-07     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  100968552     Medline TA:  BMC Med Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  S3     Citation Subset:  IM    
Affiliation:
The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA. Levyd@nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adult
Arteries / physiopathology*
Blood Pressure / genetics*
Cardiovascular Diseases / genetics*,  physiopathology
Cohort Studies
Disease Susceptibility
Female
Genetic Markers
Genome, Human*
Humans
Male
Middle Aged
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide
Pulsatile Flow
Grant Support
ID/Acronym/Agency:
1S10RR163736-01A1/RR/NCRR NIH HHS; K24-HL04334/HL/NHLBI NIH HHS; N01-HC 25195/HC/NHLBI NIH HHS; R01-HL60040/HL/NHLBI NIH HHS; R01-HL70100/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Genetic Markers
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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