Evidence map›Paper›PMID 24262325›Full record

SynthesisStroke2014

Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.

Martin Dichgans, Rainer Malik, Inke R König, Jonathan Rosand, Robert Clarke, Solveig Gretarsdottir, Gudmar Thorleifsson, Braxton D Mitchell, Themistocles L Assimes, Christopher Levi and 33 more

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

Synthesis in Stroke, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 16 pooled it
21.8field-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

191 citing papers in PubMed, 16 syntheses or guidelines pooled it, 330 citations in OpenAlex.

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131 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

43 authors at 20 institutions in 11 countries.

Martin DichgansFrom the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany (M.D., R. Malik); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.); Institut für Medizinische Biometrie und Statistik (I.R.K.), and Institut für integrative und experimentelle Genomik (J.E.), Universität zu Lübeck, Lübeck, Germany; Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany (I.R.K.); Department of Neurology and Center for Human Genetic Research (J.R.), and Cardiology Division (C.J.O.D.), Massachusetts General Hospital, Boston; Harvard Medical School, Boston, MA (J.R.); Program in Medical and Population Genetics (J.R.), and Program in Medical and Population Genetics (S.K.), Broad Institute of Harvard and MIT, Cambridge, MA; Clinical Trial Service Unit and Epidemiological Studies Unit (R.C., J.C.H.), Wellcome Trust Centre for Human Genetics (H.W., M. Farrall), Department of Cardiovascular Medicine (M. Farrall), and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; deCODE Genetics, Reykjavik, Iceland (S.G., G.T., U.T., K.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (B.D.M.); Department of Medicine, Stanford University School of Medicine, Stanford, CA (T.L.A.); Center for Translational Neuroscience and Mental Health Research, University of Newcastle, New South Wales, Australia (C.L.); Hunter Medical Research Institute, New South Wales, Australia (C.L.); National Heart, Lung and Blood Institute and NHLBI's Framingham Heart Study, MA (C.J.O.D., S.S.); University of Texas Health Science Center at Houston (M. Fornage); Cardiovascular Health Research Unit, Department of Epidemiology (B.M.P.), Department of Medicine (B.M.P.), Department of Health Services (B.M.P.), and Cardiovascular Health Research Unit, Department of Medicine (J.C.B.), University
Rainer Malik
Inke R König
Jonathan Rosand
Robert Clarke
Solveig Gretarsdottir
Gudmar Thorleifsson
Braxton D Mitchell
Themistocles L Assimes
Christopher Levi
Christopher J O'Donnell
Myriam Fornage
Unnur Thorsteinsdottir
Bruce M Psaty
Christian Hengstenberg
Sudha Seshadri
Jeanette Erdmann
Joshua C Bis
Annette Peters
Giorgio B Boncoraglio
Winfried März
James F Meschia
Sekar Kathiresan
M Arfan Ikram
Ruth McPherson
Kari Stefansson
Cathie Sudlow
Muredach P Reilly
John R Thompson
Pankaj Sharma
Jemma C Hopewell
John C Chambers
Hugh Watkins
Peter M Rothwell
Robert Roberts
Hugh S Markus
Nilesh J Samani
Martin Farrall
Heribert Schunkert
METASTROKE Consortium
CARDIoGRAM Consortium
C4D Consortium
International Stroke Genetics Consortium
Institute for Integrative and Experimental Genomics · DEdeCODE Genetics (Iceland) · ISBoston University · USBroad Institute · USCentre for Human Genetics · GBUniversity of Leeds · GBUniversity of Maryland, Baltimore · USUniversity of Ottawa · CACalifornia University of Pennsylvania · USEckert & Ziegler (United States) · USHarvard University Press · USIstituti di Ricovero e Cura a Carattere Scientifico · ITJacksonville College · USLung Institute · USSt George's, University of London · GBStihl (Germany) · DESynlab Czech (Czechia) · CZThe University of Texas Health Science Center at Houston · USUniversity Hospital Regensburg · DEUniversity of Leicester · GB

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Structural Determinants Of Ceruloplasmin Inflammatory ActivityP01HL076491 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2004 to 2019
$27.3M
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
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
UCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5M
AN NCRR CENTER FOR HIGH THROUGHPUT SNP GENOTYPING AND ANALYSIS: GAIN NETWORKU54RR020278 · NCRR · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2004 to 2008
$14.4M
Regression of Atherosclerosis CoreP01HL098055 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI FISHER, EDWARD A · 2010 to 2014
$12.1M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5U01HL096917 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI MOSLEY, THOMAS H · 2010 to 2018
$11.9M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
British Heart Foundation RE/08/004British Heart Foundation SP/04/002CIHR MOP172605CIHR MOP77682CIHR MOP-82810Intramural NIH HHS Z01 AG000015Intramural NIH HHS Z99 HL999999Intramural NIH HHS ZIA HL006002Medical Research Council G0601966Medical Research Council G0700931Medical Research Council MC_U137686857NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCRR NIH HHS U54 RR020278NCRR NIH HHS UL1 RR025005NCRR NIH HHS UL1RR025005NCRR NIH HHS UL1 RR033176NCRR NIH HHS UL1RR033176NHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01HG004402NHGRI NIH HHS U01 HG004436NHGRI NIH HHS U01 HG 004446NHGRI NIH HHS U01 HG004446NHLBI NIH HHS 1R01HL103931-01NHLBI NIH HHS HL080295NHLBI NIH HHS HL087647NHLBI NIH HHS HL087652NHLBI NIH HHS HL-093029NHLBI NIH HHS HL105756NHLBI NIH HHS HL93029NHLBI NIH HHS N01 HC025195NHLBI 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 HC075150NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085084NHLBI NIH HHS N01 HC085085NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01-HC-25195NHLBI 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-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-85086NHLBI NIH HHS N01-HC-85239NHLBI NIH HHS N02-HL-6-4278NHLBI NIH HHS P01 HL076491NHLBI NIH HHS P01HL076491-06NHLBI NIH HHS P01 HL087018NHLBI NIH HHS P01HL087018NHLBI NIH HHS P01 HL098055NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL073410NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01 HL087641NHLBI 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 HL093029NHLBI NIH HHS R01-HL093029NHLBI NIH HHS R01 HL103931NHLBI NIH HHS R01 HL105756NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL096917NIA NIH HHS AG-023629NIA NIH HHS AG-027058NIA NIH HHS AG033193NIA NIH HHS AG-20098NIA NIH HHS N01 AG012100NIA 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 AG023629NIA NIH HHS Z01 AG-000015-50NIA NIH HHS Z01 AG-000954-06NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK072488NIDDK NIH HHS R01 DK080732NIDDK NIH HHS R01DK080732NINDS NIH HHS NS17950NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS039987NINDS NIH HHS R01 NS042733NINDS NIH HHS R01 NS045012NINDS NIH HHS R01 NS-39987NINDS NIH HHS R01 NS-42733NINDS NIH HHS R01 NS45012NINDS NIH HHS U01 NS069208NINDS NIH HHS U01 NS069208-01PHS HHS HHSN268200625226CPHS HHS HHSN26820110 0008CPHS HHS HHSN268 201100011CPHS HHS R01H L59367The Dunhill Medical Trust OSRP2/1006Wellcome Trust 075491/Z/04Wellcome Trust 084723/Z/08/ZWellcome Trust 085475/B/08/ZWellcome Trust 085475/Z/08/ZWellcome Trust 090532Wellcome Trust 090532/Z/09/ZWellcome Trust 095626Wellcome Trust WT084724MA
6 · The paper itself

Abstract

background and purposeIschemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases.

methodsGenome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype.

resultsCommon variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5×10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (PIS=1.62×10(-7)) and ABO (PIS=2.6×10(-4)), as well as at HDAC9 (PLAS=2.32×10(-12)), 9p21 (PLAS=3.70×10(-6)), RAI1-PEMT-RASD1 (PLAS=2.69×10(-5)), EDNRA (PLAS=7.29×10(-4)), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10(-4)).

conclusionsOur results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.

Indexed as

Brain IschemiaCoronary Artery DiseaseData Interpretation, StatisticalGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideReproducibility of ResultsRisk FactorsStrokecoronary artery diseasegeneticsmeta-analysispolymorphism, single nucleotidestroke

Identifiers

PMID24262325
PMCPMC4112102
OpenAlexW2121187319

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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.