Evidence map›Paper›PMID 23969696›Full record

SynthesisCirculation2013

Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.

Maria Sabater-Lleal, Jie Huang, Daniel Chasman, Silvia Naitza, Abbas Dehghan, Andrew D Johnson, Alexander Teumer, Alex P Reiner, Lasse Folkersen, Saonli Basu and 140 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 15 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 15 pooled it
11.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 15 syntheses or guidelines pooled it, 149 citations in OpenAlex.

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  6. Metabolic profiling of alcohol consumption in 9778 young adults.International journal of epidemiology · 2016
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  19. Genetics of Sudden Cardiac Death.Diseases (Basel, Switzerland) · 2025
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30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

150 authors at 20 institutions in 14 countries.

Maria Sabater-Lleal
Jie Huang
Daniel Chasman
Silvia Naitza
Abbas Dehghan
Andrew D Johnson
Alexander Teumer
Alex P Reiner
Lasse Folkersen
Saonli Basu
Alicja R Rudnicka
Stella Trompet
Anders Mälarstig
Jens Baumert
Joshua C Bis
Xiuqing Guo
Jouke J Hottenga
So-Youn Shin
Lorna M Lopez
Jari Lahti
Toshiko Tanaka
Lisa R Yanek
Tiphaine Oudot-Mellakh
James F Wilson
Pau Navarro
Jennifer E Huffman
Tatijana Zemunik
Susan Redline
Reena Mehra
Drazen Pulanic
Igor Rudan
Alan F Wright
Ivana Kolcic
Ozren Polasek
Sarah H Wild
Harry Campbell
J David Curb
Robert Wallace
Simin Liu
Charles B Eaton
Diane M Becker
Lewis C Becker
Stefania Bandinelli
Katri Räikkönen
Elisabeth Widen
Aarno Palotie
Myriam Fornage
David Green
Myron Gross
Gail Davies
Sarah E Harris
David C Liewald
John M Starr
Frances M K Williams
Peter J Grant
Timothy D Spector
Rona J Strawbridge
Angela Silveira
Bengt Sennblad
Fernando Rivadeneira
Andre G Uitterlinden
Oscar H Franco
Albert Hofman
Jenny van Dongen
Gonneke Willemsen
Dorret I Boomsma
Jie Yao
Nancy Swords Jenny
Talin Haritunians
Barbara McKnight
Thomas Lumley
Kent D Taylor
Jerome I Rotter
Bruce M Psaty
Annette Peters
Christian Gieger
Thomas Illig
Anne Grotevendt
Georg Homuth
Henry Völzke
Thomas Kocher
Anuj Goel
Maria Grazia Franzosi
Udo Seedorf
Robert Clarke
Maristella Steri
Kirill V Tarasov
Serena Sanna
David Schlessinger
David J Stott
Naveed Sattar
Brendan M Buckley
Ann Rumley
Gordon D Lowe
Wendy L McArdle
Ming-Huei Chen
Geoffrey H Tofler
Jaejoon Song
Eric Boerwinkle
Aaron R Folsom
Lynda M Rose
Anders Franco-Cereceda
Martina Teichert
M Arfan Ikram
Thomas H Mosley
Steve Bevan
Martin Dichgans
Peter M Rothwell
Cathie L M Sudlow
Jemma C Hopewell
John C Chambers
Danish Saleheen
Jaspal S Kooner
John Danesh
Christopher P Nelson
Jeanette Erdmann
Muredach P Reilly
Sekar Kathiresan
Heribert Schunkert
Pierre-Emmanuel Morange
Luigi Ferrucci
Johan G Eriksson
David Jacobs
Ian J Deary
Nicole Soranzo
Jacqueline C M Witteman
Eco J C de Geus
Russell P Tracy
Caroline Hayward
Wolfgang Koenig
Francesco Cucca
J Wouter Jukema
Per Eriksson
Sudha Seshadri
Hugh S Markus
Hugh Watkins
Nilesh J Samani
VTE Consortium
STROKE Consortium
Wellcome Trust Case Control Consortium 2 (WTCCC2)
C4D Consortium
CARDIoGRAM Consortium
Henri Wallaschofski
Nicholas L Smith
David Tregouet
Paul M Ridker
Weihong Tang
David P Strachan
Anders Hamsten
Christopher J O'Donnell
Aga Khan Foundation · KGClarke University · USDrottning Silvias barn- och ungdomssjukhus · SEEaton (Taiwan) · TWElisa (Finland) · FIGrant Medical Center · USGreenwald & Associates (United States) · USHospital Prof. Dr. Fernando Fonseca · PTJacobs (United States) · USKlinikum St. Georg · DELaser Systems & Solutions of Europe (France) · FRNavarro College · USRiddet Institute · NZRoth and Rau (Germany) · DESchrodinger (United States) · USSchunk (United Kingdom) · GBShahab Danesh University · IRState Administration of Foreign Experts Affairs · CNSt. Brendan's Hospital · GBStella Therapeutics (United States) · US

Funding

NIMH Center Repository Supporting Stem Cell ResearchU24MH068457 · NIMH · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI BRZUSTOWICZ, LINDA M, KNOWLES, JAMES A · 2003 to 2024
$213.8M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
Type 1 Diabetes Genetics ConsortiumU01DK062418 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RICH, STEPHEN S. · 2002 to 2007
$59.8M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
ZINC AND CA EDTA THERAPY OF PLUMBISMM01RR000052 · NCRR · JOHNS HOPKINS UNIVERSITY · PI BELCHER, HAROLYN MILLICENT EDITH · 1985 to 2007
$37.3M
Women's Health Study: Continued Follow-upR01CA047988 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 1991 to 2014
$28.2M
Structural Determinants Of Ceruloplasmin Inflammatory ActivityP01HL076491 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2004 to 2019
$27.3M
Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
Biotechnology and Biological Sciences Research Council BB/F019394/1British Heart Foundation PG/09/022/26739British Heart Foundation RG/08/014/24067Cancer Research UKChief Scientist Office CZB/4/710Chief Scientist Office CZG/4/306Chief Scientist Office ETM/55Intramural NIH HHS Z01 HL006002Intramural NIH HHS Z99 HL999999Intramural NIH HHS ZIA HL006002Medical Research Council G0000934Medical Research Council G0700704Medical Research Council MC_PC_U127561128Medical Research Council MC_PC_U127592696Medical Research Council MC_U127592696Medical Research Council MC_U137686857Medical Research Council MC_UU_12013/1Medical Research Council MR/K026992/1Medical Research Council MR/L003120/1NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCATS NIH HHS UL1 TR000439NCI NIH HHS CA047988NCI NIH HHS R01 CA047988NCRR NIH HHS M01 RR000052NCRR NIH HHS M01-RR000052NCRR NIH HHS RR-024156NCRR NIH HHS UL1 RR024156NCRR NIH HHS UL1 RR025005NCRR NIH HHS UL1RR025005NHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01HG004402NHGRI NIH HHS U01 HG004424NHGRI NIH HHS U01-HG-004424NHGRI NIH HHS U01 HG004446NHGRI NIH HHS U01-HG-004446NHGRI NIH HHS U01 HG004729NHGRI NIH HHS U01-HG-004729NHLBI NIH HHS 1R01HL103931-01NHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HL071025-01A1NHLBI NIH HHS HL080295NHLBI NIH HHS HL080467NHLBI NIH HHS HL087647NHLBI NIH HHS HL087652NHLBI NIH HHS HL097698NHLBI NIH HHS HL105756NHLBI NIH HHS HL 463680NHLBI NIH HHS HL58625-01A1NHLBI NIH HHS HL59684NHLBI NIH HHS L30 HL097698NHLBI NIH HHS N01 HC005187NHLBI NIH HHS N01 HC015103NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC035129NHLBI NIH HHS N01 HC045133NHLBI NIH HHS N01 HC045134NHLBI NIH HHS N01 HC045204NHLBI NIH HHS N01 HC045205NHLBI NIH HHS N01 HC048047NHLBI NIH HHS N01 HC048048NHLBI NIH HHS N01 HC048049NHLBI NIH HHS N01 HC048050NHLBI NIH HHS N01-HC-05187NHLBI NIH HHS N01 HC055015NHLBI NIH HHS N01 HC055016NHLBI NIH HHS N01 HC055018NHLBI NIH HHS N01 HC055019NHLBI NIH HHS N01 HC055020NHLBI NIH HHS N01 HC055021NHLBI NIH HHS N01 HC055022NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC065226NHLBI NIH HHS N01 HC075150NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095095NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N01-HC-45204NHLBI NIH HHS N01-HC-45205NHLBI NIH HHS N01-HC-48047NHLBI NIH HHS N01-HC-48048NHLBI NIH HHS N01-HC-48049NHLBI NIH HHS N01-HC-48050NHLBI NIH HHS N01-HC-55015NHLBI NIH HHS N01-HC-55016NHLBI NIH HHS N01-HC-55018NHLBI NIH HHS N01-HC-55019NHLBI NIH HHS N01-HC-55020NHLBI NIH HHS N01-HC-55021NHLBI NIH HHS N01-HC-55022NHLBI NIH HHS N01 HC-55222NHLBI NIH HHS N01 HC 65226NHLBI NIH HHS N01-HC-65226NHLBI NIH HHS N01-HC-75150NHLBI NIH HHS N01-HC-85079NHLBI NIH HHS N01-HC-85080NHLBI NIH HHS N01-HC-85081NHLBI NIH HHS N01-HC-85082NHLBI NIH HHS N01-HC-85083NHLBI NIH HHS N01-HC-85084NHLBI NIH HHS N01-HC-85085NHLBI NIH HHS N01-HC-85086NHLBI NIH HHS N01-HC-85239NHLBI NIH HHS N01-HC-95095NHLBI NIH HHS N01 HC-95159NHLBI NIH HHS N01 HC-95160NHLBI NIH HHS N01 HC-95161NHLBI NIH HHS N01 HC-95162NHLBI NIH HHS N01 HC-95163NHLBI NIH HHS N01 HC-95164NHLBI NIH HHS N01 HC-95165NHLBI NIH HHS N01 HC-95166NHLBI NIH HHS N01 HC-95167NHLBI NIH HHS N01 HC-95168NHLBI NIH HHS N01 HC-95169NHLBI NIH HHS N02-HL-64278NHLBI NIH HHS P01 HL076491NHLBI NIH HHS P01HL076491-06NHLBI NIH HHS P01 HL087018NHLBI NIH HHS P01HL087018NHLBI NIH HHS P01 HL098055NHLBI NIH HHS R01 HL043851NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL059684NHLBI NIH HHS R01 HL071025NHLBI NIH HHS R01 HL071862NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL080467NHLBI NIH HHS R01 HL084099NHLBI NIH HHS R01-HL-084099NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01-HL085251NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01 HL087647NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL087676NHLBI NIH HHS R01 HL089650NHLBI NIH HHS R01HL089650-02NHLBI NIH HHS R01 HL103931NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL109493NHLBI NIH HHS R01HL59367NHLBI NIH HHS R01 HL 71862NHLBI NIH HHS U01 HL072518NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL72518NIA NIH HHS AG-023629NIA NIH HHS AG-027058NIA NIH HHS AG-20098NIA NIH HHS N01 AG012100NIA NIH HHS N01-AG-12109NIA NIH HHS R01 AG008122NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG027058NIA NIH HHS R01 AG033193NIA NIH HHS R56 AG020098NIA NIH HHS R56 AG023629NIDDK NIH HHS DK062418NIDDK NIH HHS DK063491NIDDK NIH HHS K24 DK080140NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK080732NIDDK NIH HHS R01DK080732NIDDK NIH HHS U01 DK062418NIMHD NIH HHS R01 MD009164NIMH NIH HHS 1RC2MH089951-01NIMH NIH HHS 1RC2MH089995-01NIMH NIH HHS MH081802NIMH NIH HHS R01 MH081802NIMH NIH HHS RC2 MH089951NIMH NIH HHS RC2 MH089995NIMH NIH HHS U24 MH068457NIMH NIH HHS U24 MH068457-06NINDS NIH HHS NS017950NINDS NIH HHS R01 NS017950NINR NIH HHS NR008153-01NINR NIH HHS NR0224103NINR NIH HHS R01 NR008153PHS HHS R01D0042157-01AWellcome Trust 068545/Z/02Wellcome Trust 075491/Z/04Wellcome Trust 076113/B/04/ZWellcome Trust 079895Wellcome Trust 085475/B/08/ZWellcome Trust 085475/Z/08/ZWellcome Trust 090532Wellcome Trust 091746/Z/10/ZWellcome Trust 095626
6 · The paper itself

Abstract

backgroundEstimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. METHODS AND

resultsWe conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism.

conclusionsWe identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.

Indexed as

Genome-Wide Association StudyAdolescentAdultAgedAged, 80 and overBlack PeopleCardiovascular DiseasesCoronary Artery DiseaseFemaleFibrinogenGenetic LociGenetic Predisposition to DiseaseHispanic or LatinoHumansMaleMiddle AgedFibrinogencardiovascular diseasesfibrinogengene expressiongenome-wide association study

Identifiers

PMID23969696
PMCPMC3842025
OpenAlexW2117292999

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.