A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Paul S de Vries; Daniel I Chasman; Maria Sabater-Lleal; Ming-Huei Chen; Jennifer E Huffman; Maristella Steri; Weihong Tang; Alexander Teumer; Riccardo E Marioni; Vera Grossmann; Jouke J Hottenga; Stella Trompet; Martina Müller-Nurasyid; Jing Hua Zhao; Jennifer A Brody; Marcus E Kleber; Xiuqing Guo; Jie Jin Wang; Paul L Auer; John R Attia; Lisa R Yanek; Tarun Veer Singh Ahluwalia; Jari Lahti; Cristina Venturini; Toshiko Tanaka; Lawrence F Bielak; Peter K Joshi; Ares Rocanin-Arjo; Ivana Kolcic; Pau Navarro; Lynda M Rose; Christopher Oldmeadow; Helene Riess; Johanna Mazur; Saonli Basu; Anuj Goel; Qiong Yang; Mohsen Ghanbari; Gonneke Willemsen; Ann Rumley; Edoardo Fiorillo; Anton J M de Craen; Anne Grotevendt; Robert Scott; Kent D Taylor; Graciela E Delgado; Jie Yao; Annette Kifley; Charles Kooperberg; Rehan Qayyum; Lorna M Lopez; Tina L Berentzen; Katri Räikkönen; Massimo Mangino; Stefania Bandinelli; Patricia A Peyser; Sarah Wild; David-Alexandre Trégouët; Alan F Wright; Jonathan Marten; Tatijana Zemunik; Alanna C Morrison; Bengt Sennblad; Geoffrey Tofler; Moniek P M de Maat; Eco J C de Geus; Gordon D Lowe; Magdalena Zoledziewska; Naveed Sattar; Harald Binder; Uwe Völker; Melanie Waldenberger; Kay-Tee Khaw; Barbara McKnight; Jie Huang; Nancy S Jenny; Elizabeth G Holliday; Lihong Qi; Mark G McEvoy; Diane M Becker; John M Starr; Antti-Pekka Sarin; Pirro G Hysi; Dena G Hernandez; Min A Jhun; Harry Campbell; Anders Hamsten; Fernando Rivadeneira; Wendy L McArdle; P Eline Slagboom; Tanja Zeller; Wolfgang Koenig; Bruce M Psaty; Talin Haritunians; Jingmin Liu; Aarno Palotie; André G Uitterlinden; David J Stott; Albert Hofman; Oscar H Franco; Ozren Polasek; Igor Rudan; Pierre-Emmanuel Morange; James F Wilson; Sharon L R Kardia; Luigi Ferrucci; Tim D Spector; Johan G Eriksson; Torben Hansen; Ian J Deary; Lewis C Becker; Rodney J Scott; Paul Mitchell; Winfried März; Nick J Wareham; Annette Peters; Andreas Greinacher; Philipp S Wild; Jan W Jukema; Dorret I Boomsma; Caroline Hayward; Francesco Cucca; Russell Tracy; Hugh Watkins; Alex P Reiner; Aaron R Folsom; Paul M Ridker; Christopher J O'Donnell; Nicholas L Smith; David P Strachan; Abbas Dehghan

doi:10.1093/hmg/ddv454

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Paul S de Vries, Daniel I Chasman, Maria Sabater-Lleal, Ming-Huei Chen, Jennifer E Huffman, Maristella Steri, Weihong Tang, Alexander Teumer, Riccardo E Marioni, Vera Grossmann, Jouke J Hottenga, Stella Trompet, Martina Müller-Nurasyid, Jing Hua Zhao, Jennifer A Brody, Marcus E Kleber, Xiuqing Guo, Jie Jin Wang, Paul L Auer, John R AttiaLisa R Yanek, Tarun Veer Singh Ahluwalia, Jari Lahti, Cristina Venturini, Toshiko Tanaka, Lawrence F Bielak, Peter K Joshi, Ares Rocanin-Arjo, Ivana Kolcic, Pau Navarro, Lynda M Rose, Christopher Oldmeadow, Helene Riess, Johanna Mazur, Saonli Basu, Anuj Goel, Qiong Yang, Mohsen Ghanbari, Gonneke Willemsen, Ann Rumley, Edoardo Fiorillo, Anton J M de Craen, Anne Grotevendt, Robert Scott, Kent D Taylor, Graciela E Delgado, Jie Yao, Annette Kifley, Charles Kooperberg, Rehan Qayyum, Lorna M Lopez, Tina L Berentzen, Katri Räikkönen, Massimo Mangino, Stefania Bandinelli, Patricia A Peyser, Sarah Wild, David-Alexandre Trégouët, Alan F Wright, Jonathan Marten, Tatijana Zemunik, Alanna C Morrison, Bengt Sennblad, Geoffrey Tofler, Moniek P M de Maat, Eco J C de Geus, Gordon D Lowe, Magdalena Zoledziewska, Naveed Sattar, Harald Binder, Uwe Völker, Melanie Waldenberger, Kay-Tee Khaw, Barbara McKnight, Jie Huang, Nancy S Jenny, Elizabeth G Holliday, Lihong Qi, Mark G McEvoy, Diane M Becker, John M Starr, Antti-Pekka Sarin, Pirro G Hysi, Dena G Hernandez, Min A Jhun, Harry Campbell, Anders Hamsten, Fernando Rivadeneira, Wendy L McArdle, P Eline Slagboom, Tanja Zeller, Wolfgang Koenig, Bruce M Psaty, Talin Haritunians, Jingmin Liu, Aarno Palotie, André G Uitterlinden, David J Stott, Albert Hofman, Oscar H Franco, Ozren Polasek, Igor Rudan, Pierre-Emmanuel Morange, James F Wilson, Sharon L R Kardia, Luigi Ferrucci, Tim D Spector, Johan G Eriksson, Torben Hansen, Ian J Deary, Lewis C Becker, Rodney J Scott, Paul Mitchell, Winfried März, Nick J Wareham, Annette Peters, Andreas Greinacher, Philipp S Wild, Jan W Jukema, Dorret I Boomsma, Caroline Hayward, Francesco Cucca, Russell Tracy, Hugh Watkins, Alex P Reiner, Aaron R Folsom, Paul M Ridker, Christopher J O'Donnell, Nicholas L Smith, David P Strachan, Abbas Dehghan

Hansen Group

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Abstract

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120,000 participants of European ancestry (95,806 participants with data on the X chromosome). Approximately 10.7 million SNPs and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci of which 18 were newly identified. There were no genome-wide significant signals on the X chromosome. The lead variants of 5 significant loci were indels. We further identified 6 additional independent signals, including 3 rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

Original language	English
Journal	Human Molecular Genetics
Volume	25
Issue number	2
Pages (from-to)	358-370
Number of pages	13
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddv454
Publication status	Published - 2016

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de Vries, P. S., Chasman, D. I., Sabater-Lleal, M., Chen, M.-H., Huffman, J. E., Steri, M., Tang, W., Teumer, A., Marioni, R. E., Grossmann, V., Hottenga, J. J., Trompet, S., Müller-Nurasyid, M., Zhao, J. H., Brody, J. A., Kleber, M. E., Guo, X., Wang, J. J., Auer, P. L., ... Dehghan, A. (2016). A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. Human Molecular Genetics, 25(2), 358-370. https://doi.org/10.1093/hmg/ddv454

de Vries, PS, Chasman, DI, Sabater-Lleal, M, Chen, M-H, Huffman, JE, Steri, M, Tang, W, Teumer, A, Marioni, RE, Grossmann, V, Hottenga, JJ, Trompet, S, Müller-Nurasyid, M, Zhao, JH, Brody, JA, Kleber, ME, Guo, X, Wang, JJ, Auer, PL, Attia, JR, Yanek, LR, Ahluwalia, TVS, Lahti, J, Venturini, C, Tanaka, T, Bielak, LF, Joshi, PK, Rocanin-Arjo, A, Kolcic, I, Navarro, P, Rose, LM, Oldmeadow, C, Riess, H, Mazur, J, Basu, S, Goel, A, Yang, Q, Ghanbari, M, Willemsen, G, Rumley, A, Fiorillo, E, de Craen, AJM, Grotevendt, A, Scott, R, Taylor, KD, Delgado, GE, Yao, J, Kifley, A, Kooperberg, C, Qayyum, R, Lopez, LM, Berentzen, TL, Räikkönen, K, Mangino, M, Bandinelli, S, Peyser, PA, Wild, S, Trégouët, D-A, Wright, AF, Marten, J, Zemunik, T, Morrison, AC, Sennblad, B, Tofler, G, de Maat, MPM, de Geus, EJC, Lowe, GD, Zoledziewska, M, Sattar, N, Binder, H, Völker, U, Waldenberger, M, Khaw, K-T, McKnight, B, Huang, J, Jenny, NS, Holliday, EG, Qi, L, McEvoy, MG, Becker, DM, Starr, JM, Sarin, A-P, Hysi, PG, Hernandez, DG, Jhun, MA, Campbell, H, Hamsten, A, Rivadeneira, F, McArdle, WL, Slagboom, PE, Zeller, T, Koenig, W, Psaty, BM, Haritunians, T, Liu, J, Palotie, A, Uitterlinden, AG, Stott, DJ, Hofman, A, Franco, OH, Polasek, O, Rudan, I, Morange, P-E, Wilson, JF, Kardia, SLR, Ferrucci, L, Spector, TD, Eriksson, JG, Hansen, T, Deary, IJ, Becker, LC, Scott, RJ, Mitchell, P, März, W, Wareham, NJ, Peters, A, Greinacher, A, Wild, PS, Jukema, JW, Boomsma, DI, Hayward, C, Cucca, F, Tracy, R, Watkins, H, Reiner, AP, Folsom, AR, Ridker, PM, O'Donnell, CJ, Smith, NL, Strachan, DP & Dehghan, A 2016, 'A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration', Human Molecular Genetics, vol. 25, no. 2, pp. 358-370. https://doi.org/10.1093/hmg/ddv454

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title = "A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration",

abstract = "Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120,000 participants of European ancestry (95,806 participants with data on the X chromosome). Approximately 10.7 million SNPs and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci of which 18 were newly identified. There were no genome-wide significant signals on the X chromosome. The lead variants of 5 significant loci were indels. We further identified 6 additional independent signals, including 3 rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.",

author = "{de Vries}, {Paul S} and Chasman, {Daniel I} and Maria Sabater-Lleal and Ming-Huei Chen and Huffman, {Jennifer E} and Maristella Steri and Weihong Tang and Alexander Teumer and Marioni, {Riccardo E} and Vera Grossmann and Hottenga, {Jouke J} and Stella Trompet and Martina M{\"u}ller-Nurasyid and Zhao, {Jing Hua} and Brody, {Jennifer A} and Kleber, {Marcus E} and Xiuqing Guo and Wang, {Jie Jin} and Auer, {Paul L} and Attia, {John R} and Yanek, {Lisa R} and Ahluwalia, {Tarun Veer Singh} and Jari Lahti and Cristina Venturini and Toshiko Tanaka and Bielak, {Lawrence F} and Joshi, {Peter K} and Ares Rocanin-Arjo and Ivana Kolcic and Pau Navarro and Rose, {Lynda M} and Christopher Oldmeadow and Helene Riess and Johanna Mazur and Saonli Basu and Anuj Goel and Qiong Yang and Mohsen Ghanbari and Gonneke Willemsen and Ann Rumley and Edoardo Fiorillo and {de Craen}, {Anton J M} and Anne Grotevendt and Robert Scott and Taylor, {Kent D} and Delgado, {Graciela E} and Jie Yao and Annette Kifley and Charles Kooperberg and Rehan Qayyum and Lopez, {Lorna M} and Berentzen, {Tina L} and Katri R{\"a}ikk{\"o}nen and Massimo Mangino and Stefania Bandinelli and Peyser, {Patricia A} and Sarah Wild and David-Alexandre Tr{\'e}gou{\"e}t and Wright, {Alan F} and Jonathan Marten and Tatijana Zemunik and Morrison, {Alanna C} and Bengt Sennblad and Geoffrey Tofler and {de Maat}, {Moniek P M} and {de Geus}, {Eco J C} and Lowe, {Gordon D} and Magdalena Zoledziewska and Naveed Sattar and Harald Binder and Uwe V{\"o}lker and Melanie Waldenberger and Kay-Tee Khaw and Barbara McKnight and Jie Huang and Jenny, {Nancy S} and Holliday, {Elizabeth G} and Lihong Qi and McEvoy, {Mark G} and Becker, {Diane M} and Starr, {John M} and Antti-Pekka Sarin and Hysi, {Pirro G} and Hernandez, {Dena G} and Jhun, {Min A} and Harry Campbell and Anders Hamsten and Fernando Rivadeneira and McArdle, {Wendy L} and Slagboom, {P Eline} and Tanja Zeller and Wolfgang Koenig and Psaty, {Bruce M} and Talin Haritunians and Jingmin Liu and Aarno Palotie and Uitterlinden, {Andr{\'e} G} and Stott, {David J} and Albert Hofman and Franco, {Oscar H} and Ozren Polasek and Igor Rudan and Pierre-Emmanuel Morange and Wilson, {James F} and Kardia, {Sharon L R} and Luigi Ferrucci and Spector, {Tim D} and Eriksson, {Johan G} and Torben Hansen and Deary, {Ian J} and Becker, {Lewis C} and Scott, {Rodney J} and Paul Mitchell and Winfried M{\"a}rz and Wareham, {Nick J} and Annette Peters and Andreas Greinacher and Wild, {Philipp S} and Jukema, {Jan W} and Boomsma, {Dorret I} and Caroline Hayward and Francesco Cucca and Russell Tracy and Hugh Watkins and Reiner, {Alex P} and Folsom, {Aaron R} and Ridker, {Paul M} and O'Donnell, {Christopher J} and Smith, {Nicholas L} and Strachan, {David P} and Abbas Dehghan",

year = "2016",

doi = "10.1093/hmg/ddv454",

language = "English",

volume = "25",

pages = "358--370",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

AU - de Vries, Paul S

AU - Chasman, Daniel I

AU - Sabater-Lleal, Maria

AU - Chen, Ming-Huei

AU - Huffman, Jennifer E

AU - Steri, Maristella

AU - Tang, Weihong

AU - Teumer, Alexander

AU - Marioni, Riccardo E

AU - Grossmann, Vera

AU - Hottenga, Jouke J

AU - Trompet, Stella

AU - Müller-Nurasyid, Martina

AU - Zhao, Jing Hua

AU - Brody, Jennifer A

AU - Kleber, Marcus E

AU - Guo, Xiuqing

AU - Wang, Jie Jin

AU - Auer, Paul L

AU - Attia, John R

AU - Yanek, Lisa R

AU - Ahluwalia, Tarun Veer Singh

AU - Lahti, Jari

AU - Venturini, Cristina

AU - Tanaka, Toshiko

AU - Bielak, Lawrence F

AU - Joshi, Peter K

AU - Rocanin-Arjo, Ares

AU - Kolcic, Ivana

AU - Navarro, Pau

AU - Rose, Lynda M

AU - Oldmeadow, Christopher

AU - Riess, Helene

AU - Mazur, Johanna

AU - Basu, Saonli

AU - Goel, Anuj

AU - Yang, Qiong

AU - Ghanbari, Mohsen

AU - Willemsen, Gonneke

AU - Rumley, Ann

AU - Fiorillo, Edoardo

AU - de Craen, Anton J M

AU - Grotevendt, Anne

AU - Scott, Robert

AU - Taylor, Kent D

AU - Delgado, Graciela E

AU - Yao, Jie

AU - Kifley, Annette

AU - Kooperberg, Charles

AU - Qayyum, Rehan

AU - Lopez, Lorna M

AU - Berentzen, Tina L

AU - Räikkönen, Katri

AU - Mangino, Massimo

AU - Bandinelli, Stefania

AU - Peyser, Patricia A

AU - Wild, Sarah

AU - Trégouët, David-Alexandre

AU - Wright, Alan F

AU - Marten, Jonathan

AU - Zemunik, Tatijana

AU - Morrison, Alanna C

AU - Sennblad, Bengt

AU - Tofler, Geoffrey

AU - de Maat, Moniek P M

AU - de Geus, Eco J C

AU - Lowe, Gordon D

AU - Zoledziewska, Magdalena

AU - Sattar, Naveed

AU - Binder, Harald

AU - Völker, Uwe

AU - Waldenberger, Melanie

AU - Khaw, Kay-Tee

AU - McKnight, Barbara

AU - Huang, Jie

AU - Jenny, Nancy S

AU - Holliday, Elizabeth G

AU - Qi, Lihong

AU - McEvoy, Mark G

AU - Becker, Diane M

AU - Starr, John M

AU - Sarin, Antti-Pekka

AU - Hysi, Pirro G

AU - Hernandez, Dena G

AU - Jhun, Min A

AU - Campbell, Harry

AU - Hamsten, Anders

AU - Rivadeneira, Fernando

AU - McArdle, Wendy L

AU - Slagboom, P Eline

AU - Zeller, Tanja

AU - Koenig, Wolfgang

AU - Psaty, Bruce M

AU - Haritunians, Talin

AU - Liu, Jingmin

AU - Palotie, Aarno

AU - Uitterlinden, André G

AU - Stott, David J

AU - Hofman, Albert

AU - Franco, Oscar H

AU - Polasek, Ozren

AU - Rudan, Igor

AU - Morange, Pierre-Emmanuel

AU - Wilson, James F

AU - Kardia, Sharon L R

AU - Ferrucci, Luigi

AU - Spector, Tim D

AU - Eriksson, Johan G

AU - Hansen, Torben

AU - Deary, Ian J

AU - Becker, Lewis C

AU - Scott, Rodney J

AU - Mitchell, Paul

AU - März, Winfried

AU - Wareham, Nick J

AU - Peters, Annette

AU - Greinacher, Andreas

AU - Wild, Philipp S

AU - Jukema, Jan W

AU - Boomsma, Dorret I

AU - Hayward, Caroline

AU - Cucca, Francesco

AU - Tracy, Russell

AU - Watkins, Hugh

AU - Reiner, Alex P

AU - Folsom, Aaron R

AU - Ridker, Paul M

AU - O'Donnell, Christopher J

AU - Smith, Nicholas L

AU - Strachan, David P

AU - Dehghan, Abbas

PY - 2016

Y1 - 2016

N2 - Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120,000 participants of European ancestry (95,806 participants with data on the X chromosome). Approximately 10.7 million SNPs and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci of which 18 were newly identified. There were no genome-wide significant signals on the X chromosome. The lead variants of 5 significant loci were indels. We further identified 6 additional independent signals, including 3 rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

AB - Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120,000 participants of European ancestry (95,806 participants with data on the X chromosome). Approximately 10.7 million SNPs and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci of which 18 were newly identified. There were no genome-wide significant signals on the X chromosome. The lead variants of 5 significant loci were indels. We further identified 6 additional independent signals, including 3 rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

U2 - 10.1093/hmg/ddv454

DO - 10.1093/hmg/ddv454

M3 - Journal article

C2 - 26561523

SN - 0964-6906

VL - 25

SP - 358

EP - 370

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 2

ER -