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, Paul L Auer, John R Attia, Lisa R YanekTarunveer 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, Gonneke Willemsen, Ann Rumley, Edoardo Fiorillo, Anton J M de Craen, Anne Grotevendt, 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, 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, Sharon L R Kardia, Luigi Ferrucci, Tim D Spector, Johan G Eriksson, Torben Hansen, Ian J Deary, Lewis C Becker, Rodney J Scott, 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

Research output: Contribution to journalArticle (Academic Journal)

32 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 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 languageEnglish
JournalHuman Molecular Genetics
DOIs
Publication statusPublished - 10 Nov 2015

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