Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Joshua C. Bis; Maryam Kavousi; Nora Franceschini; Aaron Isaacs; Gonçalo R. Abecasis; Ulf Schminke; Wendy S. Post; Albert V. Smith; L. Adrienne Cupples; Hugh S. Markus; Reinhold Schmidt; Jennifer E. Huffman; Terho Lehtimäki; Jens Baumert; Thomas Münzel; Susan R. Heckbert; Abbas Dehghan; Kari North; Ben Oostra; Steve Bevan; Eva Maria Stoegerer; Caroline Hayward; Olli Raitakari; Christa Meisinger; Arne Schillert; Serena Sanna; Henry Völzke; Yu Ching Cheng; Bolli Thorsson; Caroline S. Fox; Kenneth Rice; Fernando Rivadeneira; Vijay Nambi; Eran Halperin; Katja E. Petrovic; Leena Peltonen; H. Erich Wichmann; Renate B. Schnabel; Marcus Dörr; Afshin Parsa; Thor Aspelund; Serkalem Demissie; Sekar Kathiresan; Muredach P. Reilly; Kent Taylor; Andre Uitterlinden; David J. Couper; Matthias Sitzer; Mika Kähönen; Thomas Illig; Philipp S. Wild; Marco Orru; Jan Lüdemann; Alan R. Shuldiner; Gudny Eiriksdottir; Charles C. White; Jerome I. Rotter; Albert Hofman; Jochen Seissler; Tanja Zeller; Gianluca Usala; Florian Ernst; Lenore J. Launer; Ralph B. D'Agostino; Daniel H. O'Leary; Christie Ballantyne; Joachim Thiery; Andreas Ziegler; Edward G. Lakatta; Ravi Kumar Chilukoti; Tamara B. Harris; Philip A. Wolf; Bruce M. Psaty; Joseph F. Polak; Xia Li; Wolfgang Rathmann; Manuela Uda; Eric Boerwinkle; Norman Klopp; Helena Schmidt; James F. Wilson; Jorma Viikari; Wolfgang Koenig; Stefan Blankenberg; Anne B. Newman; Jacqueline Witteman; Gerardo Heiss; Cornelia Van Duijn; Angelo Scuteri; Georg Homuth; Braxton D. Mitchell; Vilmundur Gudnason; Christopher J. O'Donnell

doi:10.1038/ng.920

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Joshua C. Bis^*
, Maryam Kavousi
, Nora Franceschini
, Aaron Isaacs
, Gonçalo R. Abecasis
, Ulf Schminke
, Wendy S. Post
, Albert V. Smith
, L. Adrienne Cupples
, Hugh S. Markus
, Reinhold Schmidt
, Jennifer E. Huffman
, Terho Lehtimäki
, Jens Baumert
, Thomas Münzel
, Susan R. Heckbert
, Abbas Dehghan
, Kari North
, Ben Oostra
, Steve Bevan

Eva Maria Stoegerer, Caroline Hayward, Olli Raitakari, Christa Meisinger, Arne Schillert, Serena Sanna, Henry Völzke, Yu Ching Cheng, Bolli Thorsson, Caroline S. Fox, Kenneth Rice, Fernando Rivadeneira, Vijay Nambi, Eran Halperin, Katja E. Petrovic, Leena Peltonen, H. Erich Wichmann, Renate B. Schnabel, Marcus Dörr, Afshin Parsa, Thor Aspelund, Serkalem Demissie, Sekar Kathiresan, Muredach P. Reilly, Kent Taylor, Andre Uitterlinden, David J. Couper, Matthias Sitzer, Mika Kähönen, Thomas Illig, Philipp S. Wild, Marco Orru, Jan Lüdemann, Alan R. Shuldiner, Gudny Eiriksdottir, Charles C. White, Jerome I. Rotter, Albert Hofman, Jochen Seissler, Tanja Zeller, Gianluca Usala, Florian Ernst, Lenore J. Launer, Ralph B. D'Agostino, Daniel H. O'Leary, Christie Ballantyne, Joachim Thiery, Andreas Ziegler, Edward G. Lakatta, Ravi Kumar Chilukoti, Tamara B. Harris, Philip A. Wolf, Bruce M. Psaty, Joseph F. Polak, Xia Li, Wolfgang Rathmann, Manuela Uda, Eric Boerwinkle, Norman Klopp, Helena Schmidt, James F. Wilson, Jorma Viikari, Wolfgang Koenig, Stefan Blankenberg, Anne B. Newman, Jacqueline Witteman, Gerardo Heiss, Cornelia Van Duijn, Angelo Scuteri, Georg Homuth, Braxton D. Mitchell, Vilmundur Gudnason, Christopher J. O'Donnell

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

183 Scopus citations

Abstract

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.

Original language	English
Pages (from-to)	940-948
Number of pages	9
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.920
State	Published - Oct 2011

Funding

Funders	Funder number
European Commission
???publication-publication-funding-organisation-not-added???	N01HC045133
National Heart, Lung, and Blood Institute	R41HL055019, R01HL088119, ZIAHL006094, R01HL075366, R01HL059367, U01HL072515, R01HL105756, R01HL064278, R01HL087641, ZIAHL006002, R01HL087652, U01HL084729, R01HL080295, R42HL055018, R01HL086694
National Institute of Neurological Disorders and Stroke	R01NS017950
National Institute on Aging	R01AG033193, N01AG012100, R01AG018728, ZIAAG007480, R56AG023629, R01AG020098, R01AG015928, R01AG016495, R01AG027058, R01AG008122
National Institute of Diabetes and Digestive and Kidney Diseases	P30DK072488, P30DK063491
National Institute of General Medical Sciences	U01GM074518
???publication-publication-funding-organisation-not-added???	P 13180
National Human Genome Research Institute	RC2HG005581, U01HG004402
???publication-publication-funding-organisation-not-added???	050-060-810
Medical Research Council	MC_U127561128
???publication-publication-funding-organisation-not-added???	M01RR016500, M01RR000069, UL1RR025005
Seventh Framework Programme	201668
National Center for Advancing Translational Sciences	UL1TR000005

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/ng.920

Cite this

Bis, J. C., Kavousi, M., Franceschini, N., Isaacs, A., Abecasis, G. R., Schminke, U., Post, W. S., Smith, A. V., Cupples, L. A., Markus, H. S., Schmidt, R., Huffman, J. E., Lehtimäki, T., Baumert, J., Münzel, T., Heckbert, S. R., Dehghan, A., North, K., Oostra, B., ... O'Donnell, C. J. (2011). Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. Nature Genetics, 43(10), 940-948. https://doi.org/10.1038/ng.920

@article{3d008d095f7d4bbebd9430ff80467b90,

title = "Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque",

abstract = "Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.",

author = "Bis, \{Joshua C.\} and Maryam Kavousi and Nora Franceschini and Aaron Isaacs and Abecasis, \{Gon{\c c}alo R.\} and Ulf Schminke and Post, \{Wendy S.\} and Smith, \{Albert V.\} and Cupples, \{L. Adrienne\} and Markus, \{Hugh S.\} and Reinhold Schmidt and Huffman, \{Jennifer E.\} and Terho Lehtim{\"a}ki and Jens Baumert and Thomas M{\"u}nzel and Heckbert, \{Susan R.\} and Abbas Dehghan and Kari North and Ben Oostra and Steve Bevan and Stoegerer, \{Eva Maria\} and Caroline Hayward and Olli Raitakari and Christa Meisinger and Arne Schillert and Serena Sanna and Henry V{\"o}lzke and Cheng, \{Yu Ching\} and Bolli Thorsson and Fox, \{Caroline S.\} and Kenneth Rice and Fernando Rivadeneira and Vijay Nambi and Eran Halperin and Petrovic, \{Katja E.\} and Leena Peltonen and Wichmann, \{H. Erich\} and Schnabel, \{Renate B.\} and Marcus D{\"o}rr and Afshin Parsa and Thor Aspelund and Serkalem Demissie and Sekar Kathiresan and Reilly, \{Muredach P.\} and Kent Taylor and Andre Uitterlinden and Couper, \{David J.\} and Matthias Sitzer and Mika K{\"a}h{\"o}nen and Thomas Illig and Wild, \{Philipp S.\} and Marco Orru and Jan L{\"u}demann and Shuldiner, \{Alan R.\} and Gudny Eiriksdottir and White, \{Charles C.\} and Rotter, \{Jerome I.\} and Albert Hofman and Jochen Seissler and Tanja Zeller and Gianluca Usala and Florian Ernst and Launer, \{Lenore J.\} and D'Agostino, \{Ralph B.\} and O'Leary, \{Daniel H.\} and Christie Ballantyne and Joachim Thiery and Andreas Ziegler and Lakatta, \{Edward G.\} and Chilukoti, \{Ravi Kumar\} and Harris, \{Tamara B.\} and Wolf, \{Philip A.\} and Psaty, \{Bruce M.\} and Polak, \{Joseph F.\} and Xia Li and Wolfgang Rathmann and Manuela Uda and Eric Boerwinkle and Norman Klopp and Helena Schmidt and Wilson, \{James F.\} and Jorma Viikari and Wolfgang Koenig and Stefan Blankenberg and Newman, \{Anne B.\} and Jacqueline Witteman and Gerardo Heiss and Duijn, \{Cornelia Van\} and Angelo Scuteri and Georg Homuth and Mitchell, \{Braxton D.\} and Vilmundur Gudnason and O'Donnell, \{Christopher J.\}",

year = "2011",

month = oct,

doi = "10.1038/ng.920",

language = "אנגלית",

volume = "43",

pages = "940--948",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Bis, JC, Kavousi, M, Franceschini, N, Isaacs, A, Abecasis, GR, Schminke, U, Post, WS, Smith, AV, Cupples, LA, Markus, HS, Schmidt, R, Huffman, JE, Lehtimäki, T, Baumert, J, Münzel, T, Heckbert, SR, Dehghan, A, North, K, Oostra, B, Bevan, S, Stoegerer, EM, Hayward, C, Raitakari, O, Meisinger, C, Schillert, A, Sanna, S, Völzke, H, Cheng, YC, Thorsson, B, Fox, CS, Rice, K, Rivadeneira, F, Nambi, V, Halperin, E, Petrovic, KE, Peltonen, L, Wichmann, HE, Schnabel, RB, Dörr, M, Parsa, A, Aspelund, T, Demissie, S, Kathiresan, S, Reilly, MP, Taylor, K, Uitterlinden, A, Couper, DJ, Sitzer, M, Kähönen, M, Illig, T, Wild, PS, Orru, M, Lüdemann, J, Shuldiner, AR, Eiriksdottir, G, White, CC, Rotter, JI, Hofman, A, Seissler, J, Zeller, T, Usala, G, Ernst, F, Launer, LJ, D'Agostino, RB, O'Leary, DH, Ballantyne, C, Thiery, J, Ziegler, A, Lakatta, EG, Chilukoti, RK, Harris, TB, Wolf, PA, Psaty, BM, Polak, JF, Li, X, Rathmann, W, Uda, M, Boerwinkle, E, Klopp, N, Schmidt, H, Wilson, JF, Viikari, J, Koenig, W, Blankenberg, S, Newman, AB, Witteman, J, Heiss, G, Duijn, CV, Scuteri, A, Homuth, G, Mitchell, BD, Gudnason, V & O'Donnell, CJ 2011, 'Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque', Nature Genetics, vol. 43, no. 10, pp. 940-948. https://doi.org/10.1038/ng.920

TY - JOUR

T1 - Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

AU - Bis, Joshua C.

AU - Kavousi, Maryam

AU - Franceschini, Nora

AU - Isaacs, Aaron

AU - Abecasis, Gonçalo R.

AU - Schminke, Ulf

AU - Post, Wendy S.

AU - Smith, Albert V.

AU - Cupples, L. Adrienne

AU - Markus, Hugh S.

AU - Schmidt, Reinhold

AU - Huffman, Jennifer E.

AU - Lehtimäki, Terho

AU - Baumert, Jens

AU - Münzel, Thomas

AU - Heckbert, Susan R.

AU - Dehghan, Abbas

AU - North, Kari

AU - Oostra, Ben

AU - Bevan, Steve

AU - Stoegerer, Eva Maria

AU - Hayward, Caroline

AU - Raitakari, Olli

AU - Meisinger, Christa

AU - Schillert, Arne

AU - Sanna, Serena

AU - Völzke, Henry

AU - Cheng, Yu Ching

AU - Thorsson, Bolli

AU - Fox, Caroline S.

AU - Rice, Kenneth

AU - Rivadeneira, Fernando

AU - Nambi, Vijay

AU - Halperin, Eran

AU - Petrovic, Katja E.

AU - Peltonen, Leena

AU - Wichmann, H. Erich

AU - Schnabel, Renate B.

AU - Dörr, Marcus

AU - Parsa, Afshin

AU - Aspelund, Thor

AU - Demissie, Serkalem

AU - Kathiresan, Sekar

AU - Reilly, Muredach P.

AU - Taylor, Kent

AU - Uitterlinden, Andre

AU - Couper, David J.

AU - Sitzer, Matthias

AU - Kähönen, Mika

AU - Illig, Thomas

AU - Wild, Philipp S.

AU - Orru, Marco

AU - Lüdemann, Jan

AU - Shuldiner, Alan R.

AU - Eiriksdottir, Gudny

AU - White, Charles C.

AU - Rotter, Jerome I.

AU - Hofman, Albert

AU - Seissler, Jochen

AU - Zeller, Tanja

AU - Usala, Gianluca

AU - Ernst, Florian

AU - Launer, Lenore J.

AU - D'Agostino, Ralph B.

AU - O'Leary, Daniel H.

AU - Ballantyne, Christie

AU - Thiery, Joachim

AU - Ziegler, Andreas

AU - Lakatta, Edward G.

AU - Chilukoti, Ravi Kumar

AU - Harris, Tamara B.

AU - Wolf, Philip A.

AU - Psaty, Bruce M.

AU - Polak, Joseph F.

AU - Li, Xia

AU - Rathmann, Wolfgang

AU - Uda, Manuela

AU - Boerwinkle, Eric

AU - Klopp, Norman

AU - Schmidt, Helena

AU - Wilson, James F.

AU - Viikari, Jorma

AU - Koenig, Wolfgang

AU - Blankenberg, Stefan

AU - Newman, Anne B.

AU - Witteman, Jacqueline

AU - Heiss, Gerardo

AU - Duijn, Cornelia Van

AU - Scuteri, Angelo

AU - Homuth, Georg

AU - Mitchell, Braxton D.

AU - Gudnason, Vilmundur

AU - O'Donnell, Christopher J.

PY - 2011/10

Y1 - 2011/10

N2 - Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.

AB - Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.

UR - https://www.scopus.com/pages/publications/80053385049

U2 - 10.1038/ng.920

DO - 10.1038/ng.920

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 21909108

AN - SCOPUS:80053385049

SN - 1061-4036

VL - 43

SP - 940

EP - 948

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Abstract

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UN SDGs

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