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, 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

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)
Pages (from-to)358-370
Number of pages13
JournalHuman molecular genetics
Volume25
Issue number2
DOIs
StatePublished - Jan 15 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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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