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 & 111 others Lisa R. Yanek, Tarunveer S. 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, Gonnekewillemsen, 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, Lornam Lopez, Tina L. Berentzen, Katri Räikkönen, Massimomangino, 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 Sarin, Wendy L. Mcardle, P. Eline Slagboom, Tanja Zeller, Wolfgang Koenig, Brucem 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, J. Wouter 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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 single-nucleotide polymorphisms and 1.2 million indelswere examined.We identified 41 genome-wide significant fibrinogen loci; of which, 18were newly identified. Therewere no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

Original languageEnglish (US)
Article numberddv454
Pages (from-to)358-370
Number of pages13
JournalHuman Molecular Genetics
Volume25
Issue number2
DOIs
StatePublished - Jan 15 2016

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Fibrinogen
Meta-Analysis
X Chromosome
Genome
Genome-Wide Association Study
HapMap Project
Genetic Loci
Single Nucleotide Polymorphism

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

De Vries, P. S., Chasman, D. I., Sabater-Lleal, M., Chen, M. H., Huffman, J. E., Steri, M., ... Dehghan, A. (2016). A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. Human Molecular Genetics, 25(2), 358-370. [ddv454]. https://doi.org/10.1093/hmg/ddv454

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. / De Vries, Paul S.; Chasman, Daniel I.; Sabater-Lleal, Maria; Chen, Ming Huei; Huffman, Jennifer E.; Steri, Maristella; Tang, Weihong; Teumer, Alexander; Marioni, Riccardo E.; Grossmann, Vera; Hottenga, Jouke J.; Trompet, Stella; Müller-Nurasyid, Martina; Zhao, Jing Hua; Brody, Jennifer A.; Kleber, Marcus E.; Guo, Xiuqing; Wang, Jie Jin; Auer, Paul L.; Attia, John R.; Yanek, Lisa R.; Ahluwalia, Tarunveer S.; Lahti, Jari; Venturini, Cristina; Tanaka, Toshiko; Bielak, Lawrence F.; Joshi, Peter K.; Rocanin-Arjo, Ares; Kolcic, Ivana; Navarro, Pau; Rose, Lynda M.; Oldmeadow, Christopher; Riess, Helene; Mazur, Johanna; Basu, Saonli; Goel, Anuj; Yang, Qiong; Ghanbari, Mohsen; Gonnekewillemsen; Rumley, Ann; Fiorillo, Edoardo; De Craen, Anton J M; Grotevendt, Anne; Scott, Robert; Taylor, Kent D.; Delgado, Graciela E.; Yao, Jie; Kifley, Annette; Kooperberg, Charles; Qayyum, Rehan; Lopez, Lornam; Berentzen, Tina L.; Räikkönen, Katri; Massimomangino; Bandinelli, Stefania; Peyser, Patricia A.; Wild, Sarah; Trégouët, David Alexandre; Wright, Alan F.; Marten, Jonathan; Zemunik, Tatijana; Morrison, Alanna C.; Sennblad, Bengt; Tofler, Geoffrey; De Maat, Moniek P M; De Geus, Eco J C; Lowe, Gordon D.; Zoledziewska, Magdalena; Sattar, Naveed; Binder, Harald; Völker, Uwe; Waldenberger, Melanie; Khaw, Kay Tee; Mcknight, Barbara; Huang, Jie; Jenny, Nancy S.; Holliday, Elizabeth G.; Qi, Lihong; Mcevoy, Mark G.; Becker, Diane M.; Starr, John M.; Sarin, Antti Pekka; Hysi, Pirro G.; Hernandez, Dena G.; Jhun, Min A.; Campbell, Harry; Hamsten, Anders; Sarin, Fernando; Mcardle, Wendy L.; Eline Slagboom, P.; Zeller, Tanja; Koenig, Wolfgang; Psaty, Brucem; Haritunians, Talin; Liu, Jingmin; Palotie, Aarno; Uitterlinden, André G.; Stott, David J.; Hofman, Albert; Franco, Oscar H.; Polasek, Ozren; Rudan, Igor; Morange, Pierre Emmanuel; Wilson, James F.; Kardia, Sharon L R; Ferrucci, Luigi; Spector, Tim D.; Eriksson, Johan G.; Hansen, Torben; Deary, Ian J.; Becker, Lewis C.; Scott, Rodney J.; Mitchell, Paul; März, Winfried; Wareham, Nick J.; Peters, Annette; Greinacher, Andreas; Wild, Philipp S.; Wouter Jukema, J.; Boomsma, Dorret I.; Hayward, Caroline; Cucca, Francesco; Tracy, Russell; Watkins, Hugh; Reiner, Alex P.; Folsom, Aaron R.; Ridker, Paul M.; O'Donnell, Christopher J.; Smith, Nicholas L.; Strachan, David P.; Dehghan, Abbas.

In: Human Molecular Genetics, Vol. 25, No. 2, ddv454, 15.01.2016, p. 358-370.

Research output: Contribution to journalArticle

De Vries, PS, Chasman, DI, Sabater-Lleal, M, Chen, MH, 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, TS, 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, Gonnekewillemsen, Rumley, A, Fiorillo, E, De Craen, AJM, Grotevendt, A, Scott, R, Taylor, KD, Delgado, GE, Yao, J, Kifley, A, Kooperberg, C, Qayyum, R, Lopez, L, Berentzen, TL, Räikkönen, K, Massimomangino, Bandinelli, S, Peyser, PA, Wild, S, Trégouët, DA, 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, KT, Mcknight, B, Huang, J, Jenny, NS, Holliday, EG, Qi, L, Mcevoy, MG, Becker, DM, Starr, JM, Sarin, AP, Hysi, PG, Hernandez, DG, Jhun, MA, Campbell, H, Hamsten, A, Sarin, F, Mcardle, WL, Eline Slagboom, P, Zeller, T, Koenig, W, Psaty, B, Haritunians, T, Liu, J, Palotie, A, Uitterlinden, AG, Stott, DJ, Hofman, A, Franco, OH, Polasek, O, Rudan, I, Morange, PE, 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, Wouter Jukema, J, 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, ddv454, pp. 358-370. https://doi.org/10.1093/hmg/ddv454
De Vries PS, Chasman DI, Sabater-Lleal M, Chen MH, Huffman JE, Steri M et al. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. Human Molecular Genetics. 2016 Jan 15;25(2):358-370. ddv454. https://doi.org/10.1093/hmg/ddv454
De Vries, Paul S. ; Chasman, Daniel I. ; Sabater-Lleal, Maria ; Chen, Ming Huei ; Huffman, Jennifer E. ; Steri, Maristella ; Tang, Weihong ; Teumer, Alexander ; Marioni, Riccardo E. ; Grossmann, Vera ; Hottenga, Jouke J. ; Trompet, Stella ; Müller-Nurasyid, Martina ; Zhao, Jing Hua ; Brody, Jennifer A. ; Kleber, Marcus E. ; Guo, Xiuqing ; Wang, Jie Jin ; Auer, Paul L. ; Attia, John R. ; Yanek, Lisa R. ; Ahluwalia, Tarunveer S. ; Lahti, Jari ; Venturini, Cristina ; Tanaka, Toshiko ; Bielak, Lawrence F. ; Joshi, Peter K. ; Rocanin-Arjo, Ares ; Kolcic, Ivana ; Navarro, Pau ; Rose, Lynda M. ; Oldmeadow, Christopher ; Riess, Helene ; Mazur, Johanna ; Basu, Saonli ; Goel, Anuj ; Yang, Qiong ; Ghanbari, Mohsen ; Gonnekewillemsen ; Rumley, Ann ; Fiorillo, Edoardo ; De Craen, Anton J M ; Grotevendt, Anne ; Scott, Robert ; Taylor, Kent D. ; Delgado, Graciela E. ; Yao, Jie ; Kifley, Annette ; Kooperberg, Charles ; Qayyum, Rehan ; Lopez, Lornam ; Berentzen, Tina L. ; Räikkönen, Katri ; Massimomangino ; Bandinelli, Stefania ; Peyser, Patricia A. ; Wild, Sarah ; Trégouët, David Alexandre ; Wright, Alan F. ; Marten, Jonathan ; Zemunik, Tatijana ; Morrison, Alanna C. ; Sennblad, Bengt ; Tofler, Geoffrey ; De Maat, Moniek P M ; De Geus, Eco J C ; Lowe, Gordon D. ; Zoledziewska, Magdalena ; Sattar, Naveed ; Binder, Harald ; Völker, Uwe ; Waldenberger, Melanie ; Khaw, Kay Tee ; Mcknight, Barbara ; Huang, Jie ; Jenny, Nancy S. ; Holliday, Elizabeth G. ; Qi, Lihong ; Mcevoy, Mark G. ; Becker, Diane M. ; Starr, John M. ; Sarin, Antti Pekka ; Hysi, Pirro G. ; Hernandez, Dena G. ; Jhun, Min A. ; Campbell, Harry ; Hamsten, Anders ; Sarin, Fernando ; Mcardle, Wendy L. ; Eline Slagboom, P. ; Zeller, Tanja ; Koenig, Wolfgang ; Psaty, Brucem ; Haritunians, Talin ; Liu, Jingmin ; Palotie, Aarno ; Uitterlinden, André G. ; Stott, David J. ; Hofman, Albert ; Franco, Oscar H. ; Polasek, Ozren ; Rudan, Igor ; Morange, Pierre Emmanuel ; Wilson, James F. ; Kardia, Sharon L R ; Ferrucci, Luigi ; Spector, Tim D. ; Eriksson, Johan G. ; Hansen, Torben ; Deary, Ian J. ; Becker, Lewis C. ; Scott, Rodney J. ; Mitchell, Paul ; März, Winfried ; Wareham, Nick J. ; Peters, Annette ; Greinacher, Andreas ; Wild, Philipp S. ; Wouter Jukema, J. ; Boomsma, Dorret I. ; Hayward, Caroline ; Cucca, Francesco ; Tracy, Russell ; Watkins, Hugh ; Reiner, Alex P. ; Folsom, Aaron R. ; Ridker, Paul M. ; O'Donnell, Christopher J. ; Smith, Nicholas L. ; Strachan, David P. ; Dehghan, Abbas. / A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. In: Human Molecular Genetics. 2016 ; Vol. 25, No. 2. pp. 358-370.
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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 single-nucleotide polymorphisms and 1.2 million indelswere examined.We identified 41 genome-wide significant fibrinogen loci; of which, 18were newly identified. Therewere no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3{\%} of the variance in plasma fibrinogen concentration.",
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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, Tarunveer S.

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 - Gonnekewillemsen,

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, Lornam

AU - Berentzen, Tina L.

AU - Räikkönen, Katri

AU - Massimomangino,

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 - Sarin, Fernando

AU - Mcardle, Wendy L.

AU - Eline Slagboom, P.

AU - Zeller, Tanja

AU - Koenig, Wolfgang

AU - Psaty, Brucem

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 - Wouter Jukema, J.

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

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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 single-nucleotide polymorphisms and 1.2 million indelswere examined.We identified 41 genome-wide significant fibrinogen loci; of which, 18were newly identified. Therewere no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three 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 single-nucleotide polymorphisms and 1.2 million indelswere examined.We identified 41 genome-wide significant fibrinogen loci; of which, 18were newly identified. Therewere no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

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