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

JC Bis; Maryam Kavousi; N Franceschini; Aaron Isaacs; GR Abecasis; U Schminke; WS Post; AV Smith; LA Cupples; HS Markus; R Schmidt; JE Huffman; T Lehtimaki; J Baumert; T Munzel; SR Heckbert; Abbas Dehghan; K North; Ben Oostra; S Bevan; EM Stoegerer; C Hayward; O Raitakari; C Meisinger; A Schillert; S Sanna; H Volzke; YC Cheng; B Thorsson; CS Fox; K Rice; Fernando Rivadeneira; V Nambi; E Halperin; KE Petrovic; L Peltonen; HE Wichmann; RB Schnabel; M Dorr; A Parsa; T Aspelund; S Demissie; S Kathiresan; MP Reilly; K Taylor; André Uitterlinden; DJ Couper; M Sitzer; M Kahonen; T Illig; PS Wild; M Orru; J Ludemann; AR Shuldiner; G Eiriksdottir; CC White; JI Rotter; Bert Hofman; J Seissler; T Zeller; G Usala; F Ernst; LJ (Lenore) Launer; RB D'Agostino; DH O'Leary; C Ballantyne; J Thiery; A Ziegler; EG Lakatta; RK Chilukoti; TB Harris; PA Wolf; BM Psaty; JF Polak; X Li; W Rathmann; M Uda; E Boerwinkle; N Klopp; Heléna Schmidt; JF Wilson; J Viikari; W Koenig; S Blankenberg; AB Newman; JCM Witteman; G Heiss; Cornelia Duijn; A Scuteri; G Homuth; BD Mitchell; V Gudnason; CJ 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

JC Bis
, Maryam Kavousi
, N Franceschini
, Aaron Isaacs
, GR Abecasis
, U Schminke
, WS Post
, AV Smith
, LA Cupples
, HS Markus
, R Schmidt
, JE Huffman
, T Lehtimaki
, J Baumert
, T Munzel
, SR Heckbert
, Abbas Dehghan
, K North
, Ben Oostra
, S Bevan

EM Stoegerer, C Hayward, O Raitakari, C Meisinger, A Schillert, S Sanna, H Volzke, YC Cheng, B Thorsson, CS Fox, K Rice, Fernando Rivadeneira, V Nambi, E Halperin, KE Petrovic, L Peltonen, HE Wichmann, RB Schnabel, M Dorr, A Parsa, T Aspelund, S Demissie, S Kathiresan, MP Reilly, K Taylor, André Uitterlinden, DJ Couper, M Sitzer, M Kahonen, T Illig, PS Wild, M Orru, J Ludemann, AR Shuldiner, G Eiriksdottir, CC White, JI Rotter, Bert Hofman, J Seissler, T Zeller, G Usala, F Ernst, LJ (Lenore) Launer, RB D'Agostino, DH O'Leary, C Ballantyne, J Thiery, A Ziegler, EG Lakatta, RK Chilukoti, TB Harris, PA Wolf, BM Psaty, JF Polak, X Li, W Rathmann, M Uda, E Boerwinkle, N Klopp, Heléna Schmidt, JF Wilson, J Viikari, W Koenig, S Blankenberg, AB Newman, JCM Witteman, G Heiss, Cornelia Duijn, A Scuteri, G Homuth, BD Mitchell, V Gudnason, CJ O'Donnell

External organisation

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

186 Citations (Scopus)

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 x 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	Undefined/Unknown
Pages (from-to)	940-U40
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.920
Publication status	Published - 2011

UN SDGs

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

SDG 3 Good Health and Well-being

Research programs

EMC MGC-02-96-01
EMC MM-01-25-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02

Access to Document

10.1038/ng.920

http://hdl.handle.net/1765/30815

Cite this

Bis, JC., Kavousi, M., Franceschini, N., Isaacs, A., Abecasis, GR., Schminke, U., Post, WS., Smith, AV., Cupples, LA., Markus, HS., Schmidt, R., Huffman, JE., Lehtimaki, T., Baumert, J., Munzel, T., Heckbert, SR., Dehghan, A., North, K., Oostra, B., ... 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, 43(10), 940-U40. https://doi.org/10.1038/ng.920

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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 x 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 = "JC Bis and Maryam Kavousi and N Franceschini and Aaron Isaacs and GR Abecasis and U Schminke and WS Post and AV Smith and LA Cupples and HS Markus and R Schmidt and JE Huffman and T Lehtimaki and J Baumert and T Munzel and SR Heckbert and Abbas Dehghan and K North and Ben Oostra and S Bevan and EM Stoegerer and C Hayward and O Raitakari and C Meisinger and A Schillert and S Sanna and H Volzke and YC Cheng and B Thorsson and CS Fox and K Rice and Fernando Rivadeneira and V Nambi and E Halperin and KE Petrovic and L Peltonen and HE Wichmann and RB Schnabel and M Dorr and A Parsa and T Aspelund and S Demissie and S Kathiresan and MP Reilly and K Taylor and Andr{\'e} Uitterlinden and DJ Couper and M Sitzer and M Kahonen and T Illig and PS Wild and M Orru and J Ludemann and AR Shuldiner and G Eiriksdottir and CC White and JI Rotter and Bert Hofman and J Seissler and T Zeller and G Usala and F Ernst and Launer, \{LJ (Lenore)\} and RB D'Agostino and DH O'Leary and C Ballantyne and J Thiery and A Ziegler and EG Lakatta and RK Chilukoti and TB Harris and PA Wolf and BM Psaty and JF Polak and X Li and W Rathmann and M Uda and E Boerwinkle and N Klopp and Hel{\'e}na Schmidt and JF Wilson and J Viikari and W Koenig and S Blankenberg and AB Newman and JCM Witteman and G Heiss and Cornelia Duijn and A Scuteri and G Homuth and BD Mitchell and V Gudnason and CJ O'Donnell",

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Bis, JC, Kavousi, M, Franceschini, N, Isaacs, A, Abecasis, GR, Schminke, U, Post, WS, Smith, AV, Cupples, LA, Markus, HS, Schmidt, R, Huffman, JE, Lehtimaki, T, Baumert, J, Munzel, T, Heckbert, SR, Dehghan, A, North, K, Oostra, B, Bevan, S, Stoegerer, EM, Hayward, C, Raitakari, O, Meisinger, C, Schillert, A, Sanna, S, Volzke, H, Cheng, YC, Thorsson, B, Fox, CS, Rice, K, Rivadeneira, F, Nambi, V, Halperin, E, Petrovic, KE, Peltonen, L, Wichmann, HE, Schnabel, RB, Dorr, M, Parsa, A, Aspelund, T, Demissie, S, Kathiresan, S, Reilly, MP, Taylor, K, Uitterlinden, A, Couper, DJ, Sitzer, M, Kahonen, M, Illig, T, Wild, PS, Orru, M, Ludemann, J, Shuldiner, AR, Eiriksdottir, G, White, CC, Rotter, JI, Hofman, B, 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, JCM, Heiss, G, Duijn, C, 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-U40. 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, JC

AU - Kavousi, Maryam

AU - Franceschini, N

AU - Isaacs, Aaron

AU - Abecasis, GR

AU - Schminke, U

AU - Post, WS

AU - Smith, AV

AU - Cupples, LA

AU - Markus, HS

AU - Schmidt, R

AU - Huffman, JE

AU - Lehtimaki, T

AU - Baumert, J

AU - Munzel, T

AU - Heckbert, SR

AU - Dehghan, Abbas

AU - North, K

AU - Oostra, Ben

AU - Bevan, S

AU - Stoegerer, EM

AU - Hayward, C

AU - Raitakari, O

AU - Meisinger, C

AU - Schillert, A

AU - Sanna, S

AU - Volzke, H

AU - Cheng, YC

AU - Thorsson, B

AU - Fox, CS

AU - Rice, K

AU - Rivadeneira, Fernando

AU - Nambi, V

AU - Halperin, E

AU - Petrovic, KE

AU - Peltonen, L

AU - Wichmann, HE

AU - Schnabel, RB

AU - Dorr, M

AU - Parsa, A

AU - Aspelund, T

AU - Demissie, S

AU - Kathiresan, S

AU - Reilly, MP

AU - Taylor, K

AU - Uitterlinden, André

AU - Couper, DJ

AU - Sitzer, M

AU - Kahonen, M

AU - Illig, T

AU - Wild, PS

AU - Orru, M

AU - Ludemann, J

AU - Shuldiner, AR

AU - Eiriksdottir, G

AU - White, CC

AU - Rotter, JI

AU - Hofman, Bert

AU - Seissler, J

AU - Zeller, T

AU - Usala, G

AU - Ernst, F

AU - Launer, LJ (Lenore)

AU - D'Agostino, RB

AU - O'Leary, DH

AU - Ballantyne, C

AU - Thiery, J

AU - Ziegler, A

AU - Lakatta, EG

AU - Chilukoti, RK

AU - Harris, TB

AU - Wolf, PA

AU - Psaty, BM

AU - Polak, JF

AU - Li, X

AU - Rathmann, W

AU - Uda, M

AU - Boerwinkle, E

AU - Klopp, N

AU - Schmidt, Heléna

AU - Wilson, JF

AU - Viikari, J

AU - Koenig, W

AU - Blankenberg, S

AU - Newman, AB

AU - Witteman, JCM

AU - Heiss, G

AU - Duijn, Cornelia

AU - Scuteri, A

AU - Homuth, G

AU - Mitchell, BD

AU - Gudnason, V

AU - O'Donnell, CJ

PY - 2011

Y1 - 2011

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 x 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 x 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.

U2 - 10.1038/ng.920

DO - 10.1038/ng.920

M3 - Article

C2 - 21909108

SN - 1061-4036

VL - 43

SP - 940-U40

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -