Multiethnic Meta-Analysis of Genome-Wide Association Studies in > 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease

M Sabater-Lleal; J Huang; D Chasman; S Naitza; Abbas Dehghan; AD Johnson; A Teumer; AP Reiner; L Folkersen; Sreya Basu; AR Rudnicka; S Trompet; A Malarstig; J Baumert; JC Bis; XQ Guo; JJ (Jouke Jan) Hottenga; SY Shin; LM Lopez; J Lahti; T Tanaka; LR Yanek; T Oudot-Mellakh; JF Wilson; P Navarro; JE Huffman; T Zemunik; S Redline; R Mehra; D Pulanic; I Rudan; AF Wright; I Kolcic; O Polasek; SH Wild; H Campbell; JD Curb; R Wallace; SM (Simin) Liu; CB Eaton; DM Becker; LC Becker; S Bandinelli; K Raikkonen; E Widen; A Palotie; M Fornage; D Green; M Gross; G Davies; SE Harris; DC Liewald; JM Starr; FMK Williams; PJ Grant; TD Spector; RJ Strawbridge; A Silveira; B Sennblad; Fernando Rivadeneira; André Uitterlinden; OH Franco Duran; Bert Hofman; Jacques Dongen; G Willemsen; DI Boomsma; JJ Yao; NS Jenny; T Haritunians; B McKnight; T Lumley; KD Taylor; JI Rotter; BM Psaty; A Peters; C Gieger; T Illig; A Grotevendt; G Homuth; H Volzke; T Kocher; A Goel; MG Franzosi; U Seedorf; R Clarke; M Steri; KV Tarasov; S Sanna; D Schlessinger; DJ Stott; N Sattar; BM Buckley; A Rumley; GD Lowe; WL McArdle; MH Chen; GH Tofler; J Song; E Boerwinkle; AR Folsom; LM Rose; A Franco-Cereceda; Martina Teichert; Arfan Ikram; TH Mosley; S Bevan; M Dichgans; PM Rothwell; CLM Sudlow; JC Hopewell; JC Chambers; D Saleheen; JS Kooner; J Danesh; CP Nelson; J Erdmann; MP Reilly; S Kathiresan; H Schunkert; PE Morange; L Ferrucci; JG Eriksson; D Jacobs; IJ Deary; N Soranzo; JCM Witteman; EJC de Geus; RP Tracy; C Hayward; W Koenig; F Cucca; JW Jukema; P Eriksson; S Seshadri; HS Markus; H Watkins; NJ Samani; H Wallaschofski; NL Smith; D Tregouet; PM Ridker; WH Tang; DP Strachan; A Hamsten; CJ O'Donnell

doi:10.1161/CIRCULATIONAHA.113.002251

Multiethnic Meta-Analysis of Genome-Wide Association Studies in > 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease

M Sabater-Lleal, J Huang, D Chasman, S Naitza, Abbas Dehghan, AD Johnson, A Teumer, AP Reiner, L Folkersen, Sreya Basu, AR Rudnicka, S Trompet, A Malarstig, J Baumert, JC Bis, XQ Guo, JJ (Jouke Jan) Hottenga, SY Shin, LM Lopez, J LahtiT Tanaka, LR Yanek, T Oudot-Mellakh, JF Wilson, P Navarro, JE Huffman, T Zemunik, S Redline, R Mehra, D Pulanic, I Rudan, AF Wright, I Kolcic, O Polasek, SH Wild, H Campbell, JD Curb, R Wallace, SM (Simin) Liu, CB Eaton, DM Becker, LC Becker, S Bandinelli, K Raikkonen, E Widen, A Palotie, M Fornage, D Green, M Gross, G Davies, SE Harris, DC Liewald, JM Starr, FMK Williams, PJ Grant, TD Spector, RJ Strawbridge, A Silveira, B Sennblad, Fernando Rivadeneira, André Uitterlinden, OH Franco Duran, Bert Hofman, Jacques Dongen, G Willemsen, DI Boomsma, JJ Yao, NS Jenny, T Haritunians, B McKnight, T Lumley, KD Taylor, JI Rotter, BM Psaty, A Peters, C Gieger, T Illig, A Grotevendt, G Homuth, H Volzke, T Kocher, A Goel, MG Franzosi, U Seedorf, R Clarke, M Steri, KV Tarasov, S Sanna, D Schlessinger, DJ Stott, N Sattar, BM Buckley, A Rumley, GD Lowe, WL McArdle, MH Chen, GH Tofler, J Song, E Boerwinkle, AR Folsom, LM Rose, A Franco-Cereceda, Martina Teichert, Arfan Ikram, TH Mosley, S Bevan, M Dichgans, PM Rothwell, CLM Sudlow, JC Hopewell, JC Chambers, D Saleheen, JS Kooner, J Danesh, CP Nelson, J Erdmann, MP Reilly, S Kathiresan, H Schunkert, PE Morange, L Ferrucci, JG Eriksson, D Jacobs, IJ Deary, N Soranzo, JCM Witteman, EJC de Geus, RP Tracy, C Hayward, W Koenig, F Cucca, JW Jukema, P Eriksson, S Seshadri, HS Markus, H Watkins, NJ Samani, H Wallaschofski, NL Smith, D Tregouet, PM Ridker, WH Tang, DP Strachan, A Hamsten, CJ O'Donnell

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

127 Citations (Scopus)

Abstract

Background Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. Methods and Results We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases Conclusions We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.

Original language	Undefined/Unknown
Pages (from-to)	1310-1324
Number of pages	15
Journal	Circulation
Volume	128
Issue number	12
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.113.002251
Publication status	Published - 2013

Research programs

EMC MM-01-39-09-A
EMC NIHES-01-64-02
EMC NIHES-03-30-02

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

Access to Document

10.1161/CIRCULATIONAHA.113.002251

Cite this

Sabater-Lleal, M., Huang, J., Chasman, D., Naitza, S., Dehghan, A., Johnson, AD., Teumer, A., Reiner, AP., Folkersen, L., Basu, S., Rudnicka, AR., Trompet, S., Malarstig, A., Baumert, J., Bis, JC., Guo, XQ., Hottenga, JJ., Shin, SY., Lopez, LM., ... O'Donnell, CJ. (2013). Multiethnic Meta-Analysis of Genome-Wide Association Studies in > 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease. Circulation, 128(12), 1310-1324. https://doi.org/10.1161/CIRCULATIONAHA.113.002251

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title = "Multiethnic Meta-Analysis of Genome-Wide Association Studies in > 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease",

abstract = "Background Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34\% to 50\%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2\%) of its variation. Methods and Results We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases Conclusions We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.",

author = "M Sabater-Lleal and J Huang and D Chasman and S Naitza and Abbas Dehghan and AD Johnson and A Teumer and AP Reiner and L Folkersen and Sreya Basu and AR Rudnicka and S Trompet and A Malarstig and J Baumert and JC Bis and XQ Guo and Hottenga, \{JJ (Jouke Jan)\} and SY Shin and LM Lopez and J Lahti and T Tanaka and LR Yanek and T Oudot-Mellakh and JF Wilson and P Navarro and JE Huffman and T Zemunik and S Redline and R Mehra and D Pulanic and I Rudan and AF Wright and I Kolcic and O Polasek and SH Wild and H Campbell and JD Curb and R Wallace and Liu, \{SM (Simin)\} and CB Eaton and DM Becker and LC Becker and S Bandinelli and K Raikkonen and E Widen and A Palotie and M Fornage and D Green and M Gross and G Davies and SE Harris and DC Liewald and JM Starr and FMK Williams and PJ Grant and TD Spector and RJ Strawbridge and A Silveira and B Sennblad and Fernando Rivadeneira and Andr{\'e} Uitterlinden and \{Franco Duran\}, OH and Bert Hofman and Jacques Dongen and G Willemsen and DI Boomsma and JJ Yao and NS Jenny and T Haritunians and B McKnight and T Lumley and KD Taylor and JI Rotter and BM Psaty and A Peters and C Gieger and T Illig and A Grotevendt and G Homuth and H Volzke and T Kocher and A Goel and MG Franzosi and U Seedorf and R Clarke and M Steri and KV Tarasov and S Sanna and D Schlessinger and DJ Stott and N Sattar and BM Buckley and A Rumley and GD Lowe and WL McArdle and MH Chen and GH Tofler and J Song and E Boerwinkle and AR Folsom and LM Rose and A Franco-Cereceda and Martina Teichert and Arfan Ikram and TH Mosley and S Bevan and M Dichgans and PM Rothwell and CLM Sudlow and JC Hopewell and JC Chambers and D Saleheen and JS Kooner and J Danesh and CP Nelson and J Erdmann and MP Reilly and S Kathiresan and H Schunkert and PE Morange and L Ferrucci and JG Eriksson and D Jacobs and IJ Deary and N Soranzo and JCM Witteman and \{de Geus\}, EJC and RP Tracy and C Hayward and W Koenig and F Cucca and JW Jukema and P Eriksson and S Seshadri and HS Markus and H Watkins and NJ Samani and H Wallaschofski and NL Smith and D Tregouet and PM Ridker and WH Tang and DP Strachan and A Hamsten and CJ O'Donnell",

year = "2013",

doi = "10.1161/CIRCULATIONAHA.113.002251",

language = "Undefined/Unknown",

volume = "128",

pages = "1310--1324",

journal = "Circulation",

issn = "0009-7322",

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Sabater-Lleal, M, Huang, J, Chasman, D, Naitza, S, Dehghan, A, Johnson, AD, Teumer, A, Reiner, AP, Folkersen, L, Basu, S, Rudnicka, AR, Trompet, S, Malarstig, A, Baumert, J, Bis, JC, Guo, XQ, Hottenga, JJ, Shin, SY, Lopez, LM, Lahti, J, Tanaka, T, Yanek, LR, Oudot-Mellakh, T, Wilson, JF, Navarro, P, Huffman, JE, Zemunik, T, Redline, S, Mehra, R, Pulanic, D, Rudan, I, Wright, AF, Kolcic, I, Polasek, O, Wild, SH, Campbell, H, Curb, JD, Wallace, R, Liu, SM, Eaton, CB, Becker, DM, Becker, LC, Bandinelli, S, Raikkonen, K, Widen, E, Palotie, A, Fornage, M, Green, D, Gross, M, Davies, G, Harris, SE, Liewald, DC, Starr, JM, Williams, FMK, Grant, PJ, Spector, TD, Strawbridge, RJ, Silveira, A, Sennblad, B, Rivadeneira, F , Uitterlinden, A, Franco Duran, OH, Hofman, B, Dongen, J, Willemsen, G, Boomsma, DI, Yao, JJ, Jenny, NS, Haritunians, T, McKnight, B, Lumley, T, Taylor, KD, Rotter, JI, Psaty, BM, Peters, A, Gieger, C, Illig, T, Grotevendt, A, Homuth, G, Volzke, H, Kocher, T, Goel, A, Franzosi, MG, Seedorf, U, Clarke, R, Steri, M, Tarasov, KV, Sanna, S, Schlessinger, D, Stott, DJ, Sattar, N, Buckley, BM, Rumley, A, Lowe, GD, McArdle, WL, Chen, MH, Tofler, GH, Song, J, Boerwinkle, E, Folsom, AR, Rose, LM, Franco-Cereceda, A, Teichert, M, Ikram, A, Mosley, TH, Bevan, S, Dichgans, M, Rothwell, PM, Sudlow, CLM, Hopewell, JC, Chambers, JC, Saleheen, D, Kooner, JS, Danesh, J, Nelson, CP, Erdmann, J, Reilly, MP, Kathiresan, S, Schunkert, H, Morange, PE, Ferrucci, L, Eriksson, JG, Jacobs, D, Deary, IJ, Soranzo, N, Witteman, JCM, de Geus, EJC, Tracy, RP, Hayward, C, Koenig, W, Cucca, F, Jukema, JW, Eriksson, P, Seshadri, S, Markus, HS, Watkins, H, Samani, NJ, Wallaschofski, H, Smith, NL, Tregouet, D, Ridker, PM, Tang, WH, Strachan, DP, Hamsten, A & O'Donnell, CJ 2013, 'Multiethnic Meta-Analysis of Genome-Wide Association Studies in > 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease', Circulation, vol. 128, no. 12, pp. 1310-1324. https://doi.org/10.1161/CIRCULATIONAHA.113.002251

Multiethnic Meta-Analysis of Genome-Wide Association Studies in > 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease. / Sabater-Lleal, M; Huang, J; Chasman, D et al.
In: Circulation, Vol. 128, No. 12, 2013, p. 1310-1324.

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

TY - JOUR

T1 - Multiethnic Meta-Analysis of Genome-Wide Association Studies in > 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease

AU - Sabater-Lleal, M

AU - Huang, J

AU - Chasman, D

AU - Naitza, S

AU - Dehghan, Abbas

AU - Johnson, AD

AU - Teumer, A

AU - Reiner, AP

AU - Folkersen, L

AU - Basu, Sreya

AU - Rudnicka, AR

AU - Trompet, S

AU - Malarstig, A

AU - Baumert, J

AU - Bis, JC

AU - Guo, XQ

AU - Hottenga, JJ (Jouke Jan)

AU - Shin, SY

AU - Lopez, LM

AU - Lahti, J

AU - Tanaka, T

AU - Yanek, LR

AU - Oudot-Mellakh, T

AU - Wilson, JF

AU - Navarro, P

AU - Huffman, JE

AU - Zemunik, T

AU - Redline, S

AU - Mehra, R

AU - Pulanic, D

AU - Rudan, I

AU - Wright, AF

AU - Kolcic, I

AU - Polasek, O

AU - Wild, SH

AU - Campbell, H

AU - Curb, JD

AU - Wallace, R

AU - Liu, SM (Simin)

AU - Eaton, CB

AU - Becker, DM

AU - Becker, LC

AU - Bandinelli, S

AU - Raikkonen, K

AU - Widen, E

AU - Palotie, A

AU - Fornage, M

AU - Green, D

AU - Gross, M

AU - Davies, G

AU - Harris, SE

AU - Liewald, DC

AU - Starr, JM

AU - Williams, FMK

AU - Grant, PJ

AU - Spector, TD

AU - Strawbridge, RJ

AU - Silveira, A

AU - Sennblad, B

AU - Rivadeneira, Fernando

AU - Uitterlinden, André

AU - Franco Duran, OH

AU - Hofman, Bert

AU - Dongen, Jacques

AU - Willemsen, G

AU - Boomsma, DI

AU - Yao, JJ

AU - Jenny, NS

AU - Haritunians, T

AU - McKnight, B

AU - Lumley, T

AU - Taylor, KD

AU - Rotter, JI

AU - Psaty, BM

AU - Peters, A

AU - Gieger, C

AU - Illig, T

AU - Grotevendt, A

AU - Homuth, G

AU - Volzke, H

AU - Kocher, T

AU - Goel, A

AU - Franzosi, MG

AU - Seedorf, U

AU - Clarke, R

AU - Steri, M

AU - Tarasov, KV

AU - Sanna, S

AU - Schlessinger, D

AU - Stott, DJ

AU - Sattar, N

AU - Buckley, BM

AU - Rumley, A

AU - Lowe, GD

AU - McArdle, WL

AU - Chen, MH

AU - Tofler, GH

AU - Song, J

AU - Boerwinkle, E

AU - Folsom, AR

AU - Rose, LM

AU - Franco-Cereceda, A

AU - Teichert, Martina

AU - Ikram, Arfan

AU - Mosley, TH

AU - Bevan, S

AU - Dichgans, M

AU - Rothwell, PM

AU - Sudlow, CLM

AU - Hopewell, JC

AU - Chambers, JC

AU - Saleheen, D

AU - Kooner, JS

AU - Danesh, J

AU - Nelson, CP

AU - Erdmann, J

AU - Reilly, MP

AU - Kathiresan, S

AU - Schunkert, H

AU - Morange, PE

AU - Ferrucci, L

AU - Eriksson, JG

AU - Jacobs, D

AU - Deary, IJ

AU - Soranzo, N

AU - Witteman, JCM

AU - de Geus, EJC

AU - Tracy, RP

AU - Hayward, C

AU - Koenig, W

AU - Cucca, F

AU - Jukema, JW

AU - Eriksson, P

AU - Seshadri, S

AU - Markus, HS

AU - Watkins, H

AU - Samani, NJ

AU - Wallaschofski, H

AU - Smith, NL

AU - Tregouet, D

AU - Ridker, PM

AU - Tang, WH

AU - Strachan, DP

AU - Hamsten, A

AU - O'Donnell, CJ

PY - 2013

Y1 - 2013

N2 - Background Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. Methods and Results We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases Conclusions We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.

AB - Background Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. Methods and Results We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases Conclusions We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.

U2 - 10.1161/CIRCULATIONAHA.113.002251

DO - 10.1161/CIRCULATIONAHA.113.002251

M3 - Article

C2 - 23969696

SN - 0009-7322

VL - 128

SP - 1310

EP - 1324

JO - Circulation

JF - Circulation

IS - 12

ER -

Sabater-Lleal M, Huang J, Chasman D, Naitza S, Dehghan A, Johnson AD et al. Multiethnic Meta-Analysis of Genome-Wide Association Studies in > 100 000 Subjects Identifies 23 FibrinogenAssociated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease. Circulation. 2013;128(12):1310-1324. doi: 10.1161/CIRCULATIONAHA.113.002251