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 language | English |
|---|---|
| Journal | Human Molecular Genetics |
| Volume | 25 |
| Issue number | 2 |
| Pages (from-to) | 358-370 |
| Number of pages | 13 |
| ISSN | 0964-6906 |
| DOIs | |
| Publication status | Published - 2016 |
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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, Tarun Veer Singh; 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; Willemsen, Gonneke; 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, Lorna M; Berentzen, Tina L; Räikkönen, Katri; Mangino, Massimo; 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; Rivadeneira, Fernando; McArdle, Wendy L; Slagboom, P Eline; Zeller, Tanja; Koenig, Wolfgang; Psaty, Bruce M; 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; Jukema, Jan W; 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, 2016, p. 358-370.Research output: Contribution to journal › Journal article › Research › peer-review
}
TY - JOUR
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, Tarun Veer Singh
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 - Willemsen, Gonneke
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, Lorna M
AU - Berentzen, Tina L
AU - Räikkönen, Katri
AU - Mangino, Massimo
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 - Rivadeneira, Fernando
AU - McArdle, Wendy L
AU - Slagboom, P Eline
AU - Zeller, Tanja
AU - Koenig, Wolfgang
AU - Psaty, Bruce M
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 - Jukema, Jan W
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
N1 - © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
PY - 2016
Y1 - 2016
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 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.
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 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.
U2 - 10.1093/hmg/ddv454
DO - 10.1093/hmg/ddv454
M3 - Journal article
C2 - 26561523
VL - 25
SP - 358
EP - 370
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 2
ER -