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A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.


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 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 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.

SUBMITTER: de Vries PS 

PROVIDER: S-EPMC4715256 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

de Vries Paul S PS   Chasman Daniel I DI   Sabater-Lleal Maria M   Chen Ming-Huei MH   Huffman Jennifer E JE   Steri Maristella M   Tang Weihong W   Teumer Alexander A   Marioni Riccardo E RE   Grossmann Vera V   Hottenga Jouke J JJ   Trompet Stella S   Müller-Nurasyid Martina M   Zhao Jing Hua JH   Brody Jennifer A JA   Kleber Marcus E ME   Guo Xiuqing X   Wang Jie Jin JJ   Auer Paul L PL   Attia John R JR   Yanek Lisa R LR   Ahluwalia Tarunveer S TS   Lahti Jari J   Venturini Cristina C   Tanaka Toshiko T   Bielak Lawrence F LF   Joshi Peter K PK   Rocanin-Arjo Ares A   Kolcic Ivana I   Navarro Pau P   Rose Lynda M LM   Oldmeadow Christopher C   Riess Helene H   Mazur Johanna J   Basu Saonli S   Goel Anuj A   Yang Qiong Q   Ghanbari Mohsen M   Willemsen Gonneke G   Rumley Ann A   Fiorillo Edoardo E   de Craen Anton J M AJ   Grotevendt Anne A   Scott Robert R   Taylor Kent D KD   Delgado Graciela E GE   Yao Jie J   Kifley Annette A   Kooperberg Charles C   Qayyum Rehan R   Lopez Lorna M LM   Berentzen Tina L TL   Räikkönen Katri K   Mangino Massimo M   Bandinelli Stefania S   Peyser Patricia A PA   Wild Sarah S   Trégouët David-Alexandre DA   Wright Alan F AF   Marten Jonathan J   Zemunik Tatijana T   Morrison Alanna C AC   Sennblad Bengt B   Tofler Geoffrey G   de Maat Moniek P M MP   de Geus Eco J C EJ   Lowe Gordon D GD   Zoledziewska Magdalena M   Sattar Naveed N   Binder Harald H   Völker Uwe U   Waldenberger Melanie M   Khaw Kay-Tee KT   Mcknight Barbara B   Huang Jie J   Jenny Nancy S NS   Holliday Elizabeth G EG   Qi Lihong L   Mcevoy Mark G MG   Becker Diane M DM   Starr John M JM   Sarin Antti-Pekka AP   Hysi Pirro G PG   Hernandez Dena G DG   Jhun Min A MA   Campbell Harry H   Hamsten Anders A   Rivadeneira Fernando F   Mcardle Wendy L WL   Slagboom P Eline PE   Zeller Tanja T   Koenig Wolfgang W   Psaty Bruce M BM   Haritunians Talin T   Liu Jingmin J   Palotie Aarno A   Uitterlinden André G AG   Stott David J DJ   Hofman Albert A   Franco Oscar H OH   Polasek Ozren O   Rudan Igor I   Morange Pierre-Emmanuel PE   Wilson James F JF   Kardia Sharon L R SL   Ferrucci Luigi L   Spector Tim D TD   Eriksson Johan G JG   Hansen Torben T   Deary Ian J IJ   Becker Lewis C LC   Scott Rodney J RJ   Mitchell Paul P   März Winfried W   Wareham Nick J NJ   Peters Annette A   Greinacher Andreas A   Wild Philipp S PS   Jukema J Wouter JW   Boomsma Dorret I DI   Hayward Caroline C   Cucca Francesco F   Tracy Russell R   Watkins Hugh H   Reiner Alex P AP   Folsom Aaron R AR   Ridker Paul M PM   O'Donnell Christopher J CJ   Smith Nicholas L NL   Strachan David P DP   Dehghan Abbas A  

Human molecular genetics 20151110 2


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  ...[more]

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