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; CARDIoGRAM Consortium

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, CARDIoGRAM Consortium

^*Corresponding author for this work

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

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)	940-7
Number of pages	8
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.920
Publication status	Published - 11 Sept 2011
Externally published	Yes

Keywords

Adult
Aged
Aging/genetics
Atherosclerosis/genetics
Carotid Intima-Media Thickness
Cohort Studies
Coronary Artery Disease/genetics
European Continental Ancestry Group/genetics
Genetic Loci
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Genotype
Heart/physiopathology
Humans
Middle Aged
Phenotype
Plaque, Atherosclerotic/genetics
Polymorphism, Single Nucleotide
Risk Factors

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https://www.research.ed.ac.uk/en/publications/83ad794a-0341-4c60-94c7-9cd37595774cLicence: Other

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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., ... CARDIoGRAM Consortium (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), 940-7. https://doi.org/10.1038/ng.920

@article{d60c514095304f43be7860914564bae6,

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.",

keywords = "Adult, Aged, Aging/genetics, Atherosclerosis/genetics, Carotid Intima-Media Thickness, Cohort Studies, Coronary Artery Disease/genetics, European Continental Ancestry Group/genetics, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotype, Heart/physiopathology, Humans, Middle Aged, Phenotype, Plaque, Atherosclerotic/genetics, Polymorphism, Single Nucleotide, Risk Factors",

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 Eva-Maria Stoegerer and Caroline Hayward and Olli Raitakari and Christa Meisinger and Arne Schillert and Serena Sanna and Henry V{\"o}lzke and Yu-Ching Cheng 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 \{CARDIoGRAM Consortium\}",

year = "2011",

month = sep,

day = "11",

doi = "10.1038/ng.920",

language = "English",

volume = "43",

pages = "940--7",

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, E-M, Hayward, C, Raitakari, O, Meisinger, C, Schillert, A, Sanna, S, Völzke, H, Cheng, Y-C, 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 & CARDIoGRAM Consortium 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. 940-7. 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 - CARDIoGRAM Consortium

PY - 2011/9/11

Y1 - 2011/9/11

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.

KW - Adult

KW - Aged

KW - Aging/genetics

KW - Atherosclerosis/genetics

KW - Carotid Intima-Media Thickness

KW - Cohort Studies

KW - Coronary Artery Disease/genetics

KW - European Continental Ancestry Group/genetics

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Genotype

KW - Heart/physiopathology

KW - Humans

KW - Middle Aged

KW - Phenotype

KW - Plaque, Atherosclerotic/genetics

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

U2 - 10.1038/ng.920

DO - 10.1038/ng.920

M3 - Article

C2 - 21909108

SN - 1061-4036

VL - 43

SP - 940

EP - 947

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

Keywords

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