Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data
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Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. / Vasan, Ramachandran S; Glazer, Nicole L; Felix, Janine F; Lieb, Wolfgang; Wild, Philipp S; Felix, Stephan B; Watzinger, Norbert; Larson, Martin G; Smith, Nicholas L; Dehghan, Abbas; Grosshennig, Anika; Schillert, Arne; Teumer, Alexander; Schmidt, Reinhold; Kathiresan, Sekar; Lumley, Thomas; Aulchenko, Yurii S; König, Inke R; Zeller, Tanja; Homuth, Georg; Struchalin, Maksim; Aragam, Jayashri; Bis, Joshua C; Rivadeneira, Fernando; Erdmann, Jeanette; Schnabel, Renate B; Dörr, Marcus; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J; Greiser, Karin Halina; Levy, Daniel; Haritunians, Talin; Deckers, Jaap W; Stritzke, Jan; Lackner, Karl J; Völker, Uwe; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; O'Donnell, Christopher J; Heckbert, Susan R; Stricker, Bruno H; Ziegler, Andreas; Reffelmann, Thorsten; Redfield, Margaret M; Werdan, Karl; Mitchell, Gary F; Rice, Kenneth; Arnett, Donna K; Hofman, Albert; Gottdiener, John S; Uitterlinden, Andre G; Meitinger, Thomas; Blettner, Maria; Friedrich, Nele; Wang, Thomas J; Psaty, Bruce M; van Duijn, Cornelia M; Wichmann, H-Erich; Munzel, Thomas F; Kroemer, Heyo K; Benjamin, Emelia J; Rotter, Jerome I; Witteman, Jacqueline C; Schunkert, Heribert; Schmidt, Helena; Völzke, Henry; Blankenberg, Stefan.
in: JAMA-J AM MED ASSOC, Jahrgang 302, Nr. 2, 08.07.2009, S. 168-178.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data
AU - Vasan, Ramachandran S
AU - Glazer, Nicole L
AU - Felix, Janine F
AU - Lieb, Wolfgang
AU - Wild, Philipp S
AU - Felix, Stephan B
AU - Watzinger, Norbert
AU - Larson, Martin G
AU - Smith, Nicholas L
AU - Dehghan, Abbas
AU - Grosshennig, Anika
AU - Schillert, Arne
AU - Teumer, Alexander
AU - Schmidt, Reinhold
AU - Kathiresan, Sekar
AU - Lumley, Thomas
AU - Aulchenko, Yurii S
AU - König, Inke R
AU - Zeller, Tanja
AU - Homuth, Georg
AU - Struchalin, Maksim
AU - Aragam, Jayashri
AU - Bis, Joshua C
AU - Rivadeneira, Fernando
AU - Erdmann, Jeanette
AU - Schnabel, Renate B
AU - Dörr, Marcus
AU - Zweiker, Robert
AU - Lind, Lars
AU - Rodeheffer, Richard J
AU - Greiser, Karin Halina
AU - Levy, Daniel
AU - Haritunians, Talin
AU - Deckers, Jaap W
AU - Stritzke, Jan
AU - Lackner, Karl J
AU - Völker, Uwe
AU - Ingelsson, Erik
AU - Kullo, Iftikhar
AU - Haerting, Johannes
AU - O'Donnell, Christopher J
AU - Heckbert, Susan R
AU - Stricker, Bruno H
AU - Ziegler, Andreas
AU - Reffelmann, Thorsten
AU - Redfield, Margaret M
AU - Werdan, Karl
AU - Mitchell, Gary F
AU - Rice, Kenneth
AU - Arnett, Donna K
AU - Hofman, Albert
AU - Gottdiener, John S
AU - Uitterlinden, Andre G
AU - Meitinger, Thomas
AU - Blettner, Maria
AU - Friedrich, Nele
AU - Wang, Thomas J
AU - Psaty, Bruce M
AU - van Duijn, Cornelia M
AU - Wichmann, H-Erich
AU - Munzel, Thomas F
AU - Kroemer, Heyo K
AU - Benjamin, Emelia J
AU - Rotter, Jerome I
AU - Witteman, Jacqueline C
AU - Schunkert, Heribert
AU - Schmidt, Helena
AU - Völzke, Henry
AU - Blankenberg, Stefan
PY - 2009/7/8
Y1 - 2009/7/8
N2 - CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease.OBJECTIVE: 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.DESIGN, SETTING, AND PARTICIPANTS: 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.MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size.RESULTS: 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).CONCLUSIONS: 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.
AB - CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease.OBJECTIVE: 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.DESIGN, SETTING, AND PARTICIPANTS: 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.MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size.RESULTS: 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).CONCLUSIONS: 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Aorta/anatomy & histology
KW - Cardiovascular Diseases/epidemiology
KW - Echocardiography
KW - European Continental Ancestry Group
KW - Female
KW - Genome-Wide Association Study
KW - Genotype
KW - Heart Atria/anatomy & histology
KW - Heart Ventricles/anatomy & histology
KW - Humans
KW - Male
KW - Middle Aged
KW - Organ Size
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Ventricular Dysfunction, Left/genetics
KW - Ventricular Function, Left/genetics
U2 - 10.1001/jama.2009.978-a
DO - 10.1001/jama.2009.978-a
M3 - SCORING: Journal article
C2 - 19584346
VL - 302
SP - 168
EP - 178
JO - JAMA-J AM MED ASSOC
JF - JAMA-J AM MED ASSOC
SN - 0098-7484
IS - 2
ER -