Multiethnic meta-analysis of genome-wide association studies in &gt;100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

Sabater-Lleal, Maria; Huang, Jie; Chasman, Daniel; Naitza, Silvia; Dehghan, Abbas; Johnson, Andrew D.; Teumer, Alexander; Reiner, Alex P.; Folkersen, Lasse; Basu, Saonli; Rudnicka, Alicja R.; Trompet, Stella; Malarstig, A.; Mälarstig, Anders; Baumert, Jens; Bis, Joshua C.; Guo, Xiuqing; Hottenga, Jouke J.; Shin, So-Youn; Lopez, Lorna M.; Lahti, Jari; Tanaka, Toshiko; Yanek, Lisa R.; Oudot-Mellakh, Tiphaine; Wilson, James F.; Navarro, Pau; Huffman, Jennifer E.; Zemunik, Tatijana; Redline, Susan; Mehra, Reena; Pulanic, Drazen; Rudan, Igor; Wright, Alan F.; Kolcic, Ivana; Polasek, Ozren; Wild, Sarah H.; Campbell, Harry; Curb, J. David; Wallace, Robert; Liu, Simin; Eaton, Charles B.; Becker, Diane M.; Becker, Lewis C.; Bandinelli, Stefania; Raikkonen, K.; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Fornage, Myriam; Green, David; Gross, Myron; Davies, Gail; Harris, Sarah E.; Liewald, David C.; Starr, John M.; Williams, Frances M. K.; Grant, Peter J.; Spector, Timothy D.; Strawbridge, Rona J.; Silveira, Angela; Sennblad, Bengt; Rivadeneira, Fernando; Uitterlinden, Andre G.; Franco, Oscar H.; Hofman, Albert; van Dongen, Jenny; Willemsen, Gonneke; Boomsma, Dorret I.; Yao, Jie; Swords Jenny, Nancy; Haritunians, Talin; McKnight, Barbara; Lumley, Thomas; Taylor, Kent D.; Rotter, Jerome I.; Psaty, Bruce M.; Peters, Annette; Dongen, J. Van; Gieger, Christian; Illig, Thomas; Grotevendt, Anne; Homuth, Georg; Volzke, Henry; Kocher, Thomas; Jenny, N. Swords; Goel, Anuj; Franzosi, Maria Grazia; Seedorf, Udo; Clarke, Robert; Steri, Maristella; Tarasov, Kirill V.; Sanna, Serena; Schlessinger, David; Stott, David J.; Sattar, Naveed; Buckley, Brendan M.; Rumley, Ann; Lowe, Gordon D.; McArdle, Wendy L.; Chen, Ming-Huei; Tofler, Geoffrey H.; Song, Jaejoon; Boerwinkle, Eric; Folsom, Aaron R.; Rose, Lynda M.; Franco-Cereceda, Anders; Teichert, Martina; Ikram, M. Arfan; Mosley, Thomas H.; Bevan, Steve; Dichgans, Martin; Rothwell, Peter M.; Sudlow, Cathie L. M.; Hopewell, Jemma C.; Chambers, John C.; Saleheen, Danish; Kooner, Jaspal S.; Danesh, John; Nelson, Christopher P.; Erdmann, Jeanette; Reilly, Muredach P.; Kathiresan, Sekar; Schunkert, Heribert; Morange, Pierre-Emmanuel; Ferrucci, Luigi; Eriksson, Johan G.; Jacobs, David; Deary, Ian J.; Soranzo, Nicole; Witteman, Jacqueline C. M.; de Geus, Eco J. C.; Tracy, Russell P.; Hayward, Caroline; Koenig, Wolfgang; Cucca, Francesco; Jukema, J. Wouter; Eriksson, Per; Seshadri, Sudha; Markus, Hugh S.; Watkins, Hugh; Samani, Nilesh J.; Wallaschofski, Henri; Smith, Nicholas L.; Tregouet, David; Ridker, Paul M.; Tang, Weihong; Strachan, David P.; Hamsten, Anders; O'Donnell, C. J.; Jankowski, Janusz; O’Donnell, Christopher J.

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Abbas Dehghan
Sabater-Lleal et al., 2013

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@article{Sabater-Lleal2013,
  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 (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 and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P},
  author = {Sabater-Lleal, Maria and Huang, Jie and Chasman, Daniel and Naitza, Silvia and Dehghan, Abbas and Johnson, Andrew D. and Teumer, Alexander and Reiner, Alex P. and Folkersen, Lasse and Basu, Saonli and Rudnicka, Alicja R. and Trompet, Stella and Malarstig, A. and Mälarstig, Anders and Baumert, Jens and Bis, Joshua C. and Guo, Xiuqing and Hottenga, Jouke J. and Shin, So-Youn and Lopez, Lorna M. and Lahti, Jari and Tanaka, Toshiko and Yanek, Lisa R. and Oudot-Mellakh, Tiphaine and Wilson, James F. and Navarro, Pau and Huffman, Jennifer E. and Zemunik, Tatijana and Redline, Susan and Mehra, Reena and Pulanic, Drazen and Rudan, Igor and Wright, Alan F. and Kolcic, Ivana and Polasek, Ozren and Wild, Sarah H. and Campbell, Harry and Curb, J. David and Wallace, Robert and Liu, Simin and Eaton, Charles B. and Becker, Diane M. and Becker, Lewis C. and Bandinelli, Stefania and Raikkonen, K. and Räikkönen, Katri and Widen, Elisabeth and Palotie, Aarno and Fornage, Myriam and Green, David and Gross, Myron and Davies, Gail and Harris, Sarah E. and Liewald, David C. and Starr, John M. and Williams, Frances M. K. and Grant, Peter J. and Spector, Timothy D. and Strawbridge, Rona J. and Silveira, Angela and Sennblad, Bengt and Rivadeneira, Fernando and Uitterlinden, Andre G. and Franco, Oscar H. and Hofman, Albert and van Dongen, Jenny and Willemsen, Gonneke and Boomsma, Dorret I. and Yao, Jie and Swords Jenny, Nancy and Haritunians, Talin and McKnight, Barbara and Lumley, Thomas and Taylor, Kent D. and Rotter, Jerome I. and Psaty, Bruce M. and Peters, Annette and Dongen, J. Van and Gieger, Christian and Illig, Thomas and Grotevendt, Anne and Homuth, Georg and Volzke, Henry and Kocher, Thomas and Jenny, N. Swords and Goel, Anuj and Franzosi, Maria Grazia and Seedorf, Udo and Clarke, Robert and Steri, Maristella and Tarasov, Kirill V. and Sanna, Serena and Schlessinger, David and Stott, David J. and Sattar, Naveed and Buckley, Brendan M. and Rumley, Ann and Lowe, Gordon D. and McArdle, Wendy L. and Chen, Ming-Huei and Tofler, Geoffrey H. and Song, Jaejoon and Boerwinkle, Eric and Folsom, Aaron R. and Rose, Lynda M. and Franco-Cereceda, Anders and Teichert, Martina and Ikram, M. Arfan and Mosley, Thomas H. and Bevan, Steve and Dichgans, Martin and Rothwell, Peter M. and Sudlow, Cathie L. M. and Hopewell, Jemma C. and Chambers, John C. and Saleheen, Danish and Kooner, Jaspal S. and Danesh, John and Nelson, Christopher P. and Erdmann, Jeanette and Reilly, Muredach P. and Kathiresan, Sekar and Schunkert, Heribert and Morange, Pierre-Emmanuel and Ferrucci, Luigi and Eriksson, Johan G. and Jacobs, David and Deary, Ian J. and Soranzo, Nicole and Witteman, Jacqueline C. M. and de Geus, Eco J. C. and Tracy, Russell P. and Hayward, Caroline and Koenig, Wolfgang and Cucca, Francesco and Jukema, J. Wouter and Eriksson, Per and Seshadri, Sudha and Markus, Hugh S. and Watkins, Hugh and Samani, Nilesh J. and Wallaschofski, Henri and Smith, Nicholas L. and Tregouet, David and Ridker, Paul M. and Tang, Weihong and Strachan, David P. and Hamsten, Anders and O'Donnell, C. J. and Jankowski, Janusz and O’Donnell, Christopher J.},
  doi = {10.1161/circulationaha.113.002251},
  month = {jan},
  title = {Multiethnic meta-analysis of genome-wide association studies in &gt;100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease},
  url = {http://circ.ahajournals.org/content/circulationaha/128/12/1310.full.pdf},
  year = {2013}
}

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Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

Journal article published in 2013 by Maria Sabater-Lleal, Jie Huang, Daniel Chasman, Silvia Naitza, Abbas Dehghan

, Andrew D. Johnson, Alexander Teumer, Alex P. Reiner, Lasse Folkersen, Saonli Basu, Alicja R. Rudnicka

, Stella Trompet, A. Malarstig

, Anders Mälarstig, Jens Baumert and other authors. Maria Sabater-Lleal, Jie Huang, Daniel Chasman, Silvia Naitza, Abbas Dehghan

, Andrew D. Johnson, Alexander Teumer, Alex P. Reiner, Lasse Folkersen, Saonli Basu, Alicja R. Rudnicka

, Stella Trompet, A. Malarstig

, Anders Mälarstig, Jens Baumert, Joshua C. Bis, Xiuqing Guo, Jouke J. Hottenga, So-Youn Shin, Lorna M. Lopez, Jari Lahti

, Toshiko Tanaka, Lisa R. Yanek, Tiphaine Oudot-Mellakh, James F. Wilson, Pau Navarro, Jennifer E. Huffman, Tatijana Zemunik, Susan Redline, Reena Mehra

, Drazen Pulanic, Igor Rudan, Alan F. Wright, Ivana Kolcic, Ozren Polasek, Sarah H. Wild, Harry Campbell, J. David Curb, Robert Wallace, Simin Liu, Charles B. Eaton, Diane M. Becker, Lewis C. Becker, Stefania Bandinelli, K. Raikkonen, Katri Räikkönen, Elisabeth Widen, Aarno Palotie, Myriam Fornage, David Green, Myron Gross, Gail Davies, Sarah E. Harris, David C. Liewald, John M. Starr, Frances M. K. Williams, Peter J. Grant, Timothy D. Spector, Rona J. Strawbridge, Angela Silveira, Bengt Sennblad, Fernando Rivadeneira, Andre G. Uitterlinden, Oscar H. Franco, Albert Hofman, Jenny van Dongen, Gonneke Willemsen, Dorret I. Boomsma, Jie Yao, Nancy Swords Jenny, Talin Haritunians, Barbara McKnight, Thomas Lumley, Kent D. Taylor, Jerome I. Rotter, Bruce M. Psaty, Annette Peters, J. Van Dongen, Christian Gieger

, Thomas Illig, Anne Grotevendt, Georg Homuth, Henry Volzke, Thomas Kocher, N. Swords Jenny, Anuj Goel, Maria Grazia Franzosi, Udo Seedorf

, Robert Clarke, Maristella Steri, Kirill V. Tarasov, Serena Sanna, David Schlessinger, David J. Stott, Naveed Sattar, Brendan M. Buckley, Ann Rumley, Gordon D. Lowe, Wendy L. McArdle, Ming-Huei Chen, Geoffrey H. Tofler, Jaejoon Song, Eric Boerwinkle, Aaron R. Folsom, Lynda M. Rose, Anders Franco-Cereceda, Martina Teichert, M. Arfan Ikram

, Thomas H. Mosley, Steve Bevan, Martin Dichgans, Peter M. Rothwell, Cathie L. M. Sudlow, Jemma C. Hopewell, John C. Chambers, Danish Saleheen, Jaspal S. Kooner, John Danesh, Christopher P. Nelson, Jeanette Erdmann, Muredach P. Reilly, Sekar Kathiresan, Heribert Schunkert, Pierre-Emmanuel Morange, Luigi Ferrucci, Johan G. Eriksson, David Jacobs, Ian J. Deary, Nicole Soranzo, Jacqueline C. M. Witteman, Eco J. C. de Geus, Russell P. Tracy, Caroline Hayward, Wolfgang Koenig, Francesco Cucca, J. Wouter Jukema, Per Eriksson, Sudha Seshadri, Hugh S. Markus, Hugh Watkins, Nilesh J. Samani, Henri Wallaschofski, Nicholas L. Smith, David Tregouet, Paul M. Ridker, Weihong Tang, David P. Strachan, Anders Hamsten, C. J. O'Donnell, Janusz Jankowski, Christopher J. O’Donnell

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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 (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 and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P

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