CHS Home | Welcome New Investigators | Directory | Contact Us

 

You are here

Home

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

Tuesday,2012-11-06 12:18 America/Los_Angeles — eenright
TitleGenetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.
Publication TypeJournal Article
Year of Publication2009
AuthorsVasan, RS, Glazer, NL, Felix, JF, Lieb, W, Wild, PS, Felix, SB, Watzinger, N, Larson, MG, Smith, NL, Dehghan, A, Grosshennig, A, Schillert, A, Teumer, A, Schmidt, R, Kathiresan, S, Lumley, T, Aulchenko, YS, König, IR, Zeller, T, Homuth, G, Struchalin, M, Aragam, J, Bis, JC, Rivadeneira, F, Erdmann, J, Schnabel, RB, Dörr, M, Zweiker, R, Lind, L, Rodeheffer, RJ, Greiser, KHalina, Levy, D, Haritunians, T, Deckers, JW, Stritzke, J, Lackner, KJ, Völker, U, Ingelsson, E, Kullo, I, Haerting, J, O'Donnell, CJ, Heckbert, SR, Stricker, BH, Ziegler, A, Reffelmann, T, Redfield, MM, Werdan, K, Mitchell, GF, Rice, K, Arnett, DK, Hofman, A, Gottdiener, JS, Uitterlinden, AG, Meitinger, T, Blettner, M, Friedrich, N, Wang, TJ, Psaty, BM, van Duijn, CM, Wichmann, H-E, Munzel, TF, Kroemer, HK, Benjamin, EJ, Rotter, JI, Witteman, JC, Schunkert, H, Schmidt, H, Völzke, H, Blankenberg, S
JournalJAMA
Volume302
Issue2
Pagination168-78
Date Published2009 Jul 08
ISSN1538-3598
KeywordsAdult, Aged, Aged, 80 and over, Aorta, Cardiovascular Diseases, Echocardiography, European Continental Ancestry Group, Female, Genome-Wide Association Study, Genotype, Heart Atria, Heart Ventricles, Humans, Male, Middle Aged, Organ Size, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Ventricular Dysfunction, Left, Ventricular Function, Left
Abstract<p><b>CONTEXT: </b>Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease.</p><p><b>OBJECTIVE: </b>To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples.</p><p><b>DESIGN, SETTING, AND PARTICIPANTS: </b>Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort.</p><p><b>MAIN OUTCOME MEASURES: </b>Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size.</p><p><b>RESULTS: </b>In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance).</p><p><b>CONCLUSIONS: </b>We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.</p>
DOI10.1001/jama.2009.978-a
Alternate JournalJAMA
PubMed ID19584346
PubMed Central IDPMC2975567
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
M01 RR000069-43 / RR / NCRR NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
R01HL077477 / HL / NHLBI NIH HHS / United States
R01 HL087652-03 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
R01 HL055502 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
M01 RR000069 / RR / NCRR NIH HHS / United States
N01 HC085083 / HC / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 HL077477 / HL / NHLBI NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 HL080124-05 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R01 HL093328-02 / HL / NHLBI NIH HHS / United States
2K24HL04334 / HL / NHLBI NIH HHS / United States
U01 HL080295-03 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
P 20545 / / Austrian Science Fund FWF / Austria
K24 HL004334-03 / HL / NHLBI NIH HHS / United States
R01 DK033651 / DK / NIDDK NIH HHS / United States
K24 HL004334 / HL / NHLBI NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
R01HL093328 / HL / NHLBI NIH HHS / United States
R01 HL077477-01 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
R01HL080124 / HL / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
R01 HL55502 / HL / NHLBI NIH HHS / United States
M01RR00069 / RR / NCRR NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
R01 HL093328 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
P30 DK063491-08 / DK / NIDDK NIH HHS / United States
R01 HL080124 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 HL055502-07 / HL / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States

© 2001 - 2020 CHS Coordinating Center University of Washington, Seattle, WA

Privacy | Terms