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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, 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*
*Corresponding author for this work
  • Erasmus University Rotterdam
  • Brigham and Women’s Hospital
  • Harvard University
  • Karolinska Institutet
  • Boston University
  • National Institutes of Health
  • University of Edinburgh
  • National Research Council of Italy
  • University of Minnesota Twin Cities
  • University of Greifswald
  • University of Queensland
  • Johannes Gutenberg University Mainz
  • Vrije Universiteit Amsterdam
  • Leiden University
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • Ludwig Maximilian University of Munich
  • German Centre for Cardiovascular Research
  • University of Cambridge
  • University of Washington
  • Heidelberg University 
  • University of California at Los Angeles
  • The University of Sydney
  • University of Wisconsin-Milwaukee
  • Hunter Medical Research Institute, Australia
  • University of Newcastle
  • Johns Hopkins University
  • University of Copenhagen
  • University of Helsinki
  • Folkhalsan
  • University College London
  • King's College London
  • University of Michigan, Ann Arbor
  • Institut national de la santé et de la recherche médicale
  • Sorbonne Université
  • ICAN Institute for Cardiometabolism and Nutrition
  • University of Split
  • University of Oxford
  • Mashhad University of Medical Sciences
  • University of Glasgow
  • Fred Hutchinson Cancer Research Center
  • Royal College of Surgeons in Ireland
  • University College Dublin
  • Azienda Sanitaria Firenze
  • University of Texas Health Science Center at Houston
  • VU University Medical Center
  • Wellcome Trust Sanger Institute
  • University of Vermont
  • University of California at Davis
  • National Institute for Health and Welfare
  • University of Bristol
  • University of Hamburg
  • Ulm University
  • Technical University of Munich
  • Group Health Cooperative
  • Cedars-Sinai Medical Center
  • CHU la Timone
  • Aix-Marseille Université
  • Helsinki University Hospital
  • SYNLAB International GmbH
  • Medical University of Graz
  • Durrer Center for Cardiovascular Research
  • Interuniversity Cardiology Institute of the Netherlands
  • Massachusetts General Hospital
  • Seattle Epidemiologic Research and Information Center
  • St. George's University of London

Research output: Contribution to journalArticlepeer-review

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
Pages (from-to)358-370
Number of pages13
JournalHuman Molecular Genetics
Volume25
Issue number2
DOIs
Publication statusPublished - 15 Jan 2016
Externally publishedYes

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