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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, Vol. 302, No. 2, 08.07.2009, p. 168-178.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Vasan, 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, KH, 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 2009, 'Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data', JAMA-J AM MED ASSOC, vol. 302, no. 2, pp. 168-178. https://doi.org/10.1001/jama.2009.978-a

APA

Vasan, R. S., Glazer, N. L., Felix, J. F., Lieb, W., Wild, P. S., Felix, S. B., Watzinger, N., Larson, M. G., Smith, N. L., Dehghan, A., Grosshennig, A., Schillert, A., Teumer, A., Schmidt, R., Kathiresan, S., Lumley, T., Aulchenko, Y. S., König, I. R., Zeller, T., ... Blankenberg, S. (2009). Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. JAMA-J AM MED ASSOC, 302(2), 168-178. https://doi.org/10.1001/jama.2009.978-a

Vancouver

Vasan RS, Glazer NL, Felix JF, Lieb W, Wild PS, Felix SB et al. Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. JAMA-J AM MED ASSOC. 2009 Jul 8;302(2):168-178. https://doi.org/10.1001/jama.2009.978-a

Bibtex

@article{2ba8504518df4dbeb871bdb209c1a19d,
title = "Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data",
abstract = "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.",
keywords = "Adult, Aged, Aged, 80 and over, Aorta/anatomy & histology, Cardiovascular Diseases/epidemiology, Echocardiography, European Continental Ancestry Group, Female, Genome-Wide Association Study, Genotype, Heart Atria/anatomy & histology, Heart Ventricles/anatomy & histology, Humans, Male, Middle Aged, Organ Size, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Ventricular Dysfunction, Left/genetics, Ventricular Function, Left/genetics",
author = "Vasan, {Ramachandran S} and Glazer, {Nicole L} and Felix, {Janine F} and Wolfgang Lieb and Wild, {Philipp S} and Felix, {Stephan B} and Norbert Watzinger and Larson, {Martin G} and Smith, {Nicholas L} and Abbas Dehghan and Anika Grosshennig and Arne Schillert and Alexander Teumer and Reinhold Schmidt and Sekar Kathiresan and Thomas Lumley and Aulchenko, {Yurii S} and K{\"o}nig, {Inke R} and Tanja Zeller and Georg Homuth and Maksim Struchalin and Jayashri Aragam and Bis, {Joshua C} and Fernando Rivadeneira and Jeanette Erdmann and Schnabel, {Renate B} and Marcus D{\"o}rr and Robert Zweiker and Lars Lind and Rodeheffer, {Richard J} and Greiser, {Karin Halina} and Daniel Levy and Talin Haritunians and Deckers, {Jaap W} and Jan Stritzke and Lackner, {Karl J} and Uwe V{\"o}lker and Erik Ingelsson and Iftikhar Kullo and Johannes Haerting and O'Donnell, {Christopher J} and Heckbert, {Susan R} and Stricker, {Bruno H} and Andreas Ziegler and Thorsten Reffelmann and Redfield, {Margaret M} and Karl Werdan and Mitchell, {Gary F} and Kenneth Rice and Arnett, {Donna K} and Albert Hofman and Gottdiener, {John S} and Uitterlinden, {Andre G} and Thomas Meitinger and Maria Blettner and Nele Friedrich and Wang, {Thomas J} and Psaty, {Bruce M} and {van Duijn}, {Cornelia M} and H-Erich Wichmann and Munzel, {Thomas F} and Kroemer, {Heyo K} and Benjamin, {Emelia J} and Rotter, {Jerome I} and Witteman, {Jacqueline C} and Heribert Schunkert and Helena Schmidt and Henry V{\"o}lzke and Stefan Blankenberg",
year = "2009",
month = jul,
day = "8",
doi = "10.1001/jama.2009.978-a",
language = "English",
volume = "302",
pages = "168--178",
journal = "JAMA-J AM MED ASSOC",
issn = "0098-7484",
publisher = "American Medical Association",
number = "2",

}

RIS

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 -