Evidence map›Paper›PMID 24474739›Full record

SynthesisEuropean heart journal2015

Mendelian randomization of blood lipids for coronary heart disease.

Michael V Holmes, Folkert W Asselbergs, Tom M Palmer, Fotios Drenos, Matthew B Lanktree, Christopher P Nelson, Caroline E Dale, Sandosh Padmanabhan, Chris Finan, Daniel I Swerdlow and 59 more

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

Synthesis in European heart journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 387 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
387citing papers in PubMed, 10 pooled it
39.0field-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

387 citing papers in PubMed, 10 syntheses or guidelines pooled it, 781 citations in OpenAlex.

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327 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

69 authors at 20 institutions in 6 countries.

Michael V HolmesGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK Division of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA mvholmes@gmail.com.
Folkert W AsselbergsDepartment of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK.
Tom M PalmerDivision of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
Fotios DrenosCentre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, London WC1E 6JF, UK MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Matthew B LanktreeDepartment of Medicine, McMaster University, Hamilton, ON, Canada L8S 4L8.
Christopher P NelsonDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Caroline E DaleFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Sandosh PadmanabhanInstitute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Chris FinanGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
Daniel I SwerdlowGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
Vinicius TraganteDepartment of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands Department of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Erik P A van IperenDurrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands.
Suthesh SivapalaratnamDepartment of Vascular Medicine, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.
Sonia ShahDepartment of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK.
Clara C ElbersDepartment of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Tina ShahGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
Jorgen EngmannGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
Claudia GiambartolomeiDepartment of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK.
Jon WhiteDepartment of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK.
Delilah ZabanehDepartment of Genetics Environment and Evolution, UCL Genetics Institute, 2nd Floor, Darwin Building, Gower Street, London WC1E 6BT, UK.
Reecha SofatGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
Stela McLachlanCentre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
UCLEB consortium
Pieter A DoevendansDepartment of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Anthony J BalmforthLeeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.
Alistair S HallLeeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.
Kari E NorthDepartment of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Berta AlmogueraCenter for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Ron C HoogeveenBaylor College of Medicine, Department of Medicine, Division of Atherosclerosis and Vascular Medicine, Houston, TX 77030, USA.
Mary CushmanDepartment of Medicine, University of Vermont, 208 South Park Dr, Colchester, VT 05446, USA Department of Pathology, University of Vermont, 208 South Park Dr, Colchester, VT 05446, USA.
Myriam FornageThe University of Texas Health Science Center at Houston, Houston, TX, USA.
Sanjay R PatelDepartment of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Susan RedlineDepartment of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
David S SiscovickCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA Department of Epidemiology, University of Washington, Seattle, WA, USA.
Michael Y TsaiDepartment of Laboratory Medicine and Pathology, University of Minnesota.
Konrad J KarczewskiDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Marten H HofkerDepartment Pathology and Medical Biology, Medical Biology Division, Molecular Genetics, University Medical Center Groningen and Groningen University, Groningen, The Netherlands.
W Monique VerschurenCentre for Prevention and Health Services Research at National Institute for Public Health and the Environment, Utrecht, The Netherlands.
Michiel L BotsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Yvonne T van der SchouwJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Olle MelanderLund University, Malmö, Sweden.
Anna F DominiczakInstitute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Richard MorrisDepartment of Primary Care and Population Health, UCL, Royal Free Campus, Rowland Hill St, London, UK.
Yoav Ben-ShlomoSchool of Social and Community Medicine, University of Bristol.
Jackie PriceCentre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
Meena KumariGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
Jens BaumertInstitute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Annette PetersInstitute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Barbara ThorandInstitute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Wolfgang KoenigDepartment of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany.
Tom R GauntMRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Steve E HumphriesCentre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, London WC1E 6JF, UK.
Robert ClarkeClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Hugh WatkinsDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Martin FarrallDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
Paul I W de BakkerDepartment of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Leslie A LangeDepartment of Genetics, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill,NC27514, USA.
George Davey SmithMRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Alex P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Philippa J TalmudCentre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, London WC1E 6JF, UK.
Mika KivimäkiDepartment of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
Debbie A LawlorMRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
Frank DudbridgeFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Brendan J KeatingDivision of Transplant Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104, USA Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Paediatrics, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Aroon D HingoraniGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK.
Juan P CasasGenetic Epidemiology Group, Institute of Cardiovacular Science, Faculty of Population Healh Sciences, University College London, 1-19 Torrington Place, London WC1E 6BT, UK Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
University College London · GBUniversity Medical Center Utrecht · NLUniversity of Bristol · GBChildren's Hospital of Philadelphia · USHelmholtz Zentrum München · DEUniversity of Oxford · GBAcademic Medical Center · NLBrigham and Women's Hospital · USUniversity of Edinburgh · GBUniversity of Glasgow · GBUniversity of Leeds · GBUniversity of Leicester · GBUniversity of North Carolina at Chapel Hill · USBaylor College of Medicine · USFred Hutch Cancer Center · USJackson Memorial Hospital · USLondon School of Hygiene & Tropical Medicine · GBLund University · SEMcMaster University · CANational Institute for Public Health and the Environment · NL

Funding

Project-001R01AG017644 · NIA · UNIVERSITY OF LONDON INST OF NEUROLOGY · PI Andrew Steptoe · 2000 to 2026
$56.2M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
Women's Health Initiative Memory Study (WHIMS)N01WH44221 · WH · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2009 to 2010
$3.1M
Socioeconomic gradient in CHD in early old ageR01HL036310 · NHLBI · UNIVERSITY OF LONDON · PI KIVIMAKI, MIKA J, MARMOT, MICHAEL G · 1986 to 2012
$3.1M
BLOOD COAGULATION &FIBRINOLYSISR01HL065226 · NHLBI · SCRIPPS RESEARCH INSTITUTE · PI MACKMAN, NIGEL · 2000 to 2004
$1.8M
VANGUARD CENTER FOR WOMEN'S HEALTH INITIATIVEN01WH032111 · WH · EMORY UNIVERSITY · PI WATTS, NELSON · 1993 to 2001
$1.6M
Adjunctive Use of Apyrase to Fibrinolytic TherapyR44HL095169 · NHLBI · APT THERAPEUTICS, INC. · PI CHEN, RIDONG · 2012 to 2013
$1.3M
WOMENS HEALTH INITIATIVE-N01WH22110N01WH022110 · WH · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ROSS, PRENTICE · 1992 to 2006
$1.2M
VANGUARD CENTER FOR WOMEN'S HEALTH INITIATIVEN01WH032105 · WH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LEWIS, CORA E · 1993 to 2000
$1.2M
VANGUARD CENTER FOR WOMENS HEALTH INITIATIVEN01WH032100 · WH · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERESFORD, SHIRLEY AA · 1993 to 2001
$1.1M
COMMUNITY AND COHORT SURVEILLANCE PROGRAMS-N01HC55015N01HC055015 · HC · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI CHAMBLESS, LLOYD E · 1985 to 2006
$1.1M
VANGUARD CENTER FOR WOMEN'S HEALTH INITIATIVEN01WH032118 · WH · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI JOHNSON, KAREN C · 1993 to 2000
$992k
British Heart Foundation CH/98001British Heart Foundation PG/07/131/24254British Heart Foundation PG/07/133/24260British Heart Foundation PG/13/66/30442British Heart Foundation RG/07/005/23633British Heart Foundation RG 08/008British Heart Foundation RG/08/008/25291British Heart Foundation RG/10/12/28456British Heart Foundation RG/13/16/30528British Heart Foundation RG/13/2/30098Chief Scientist Office CZB/4/672Department of HealthMedical Research Council G0802432Medical Research Council G1000718Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/5Medical Research Council MC_UU_12013/8Medical Research Council MC_UU_12019/1Medical Research Council MR/K006215/1Medical Research Council MR/K006584/1Medical Research Council MR/K013351/1Medical Research Council MR/L01629X/1NCRR NIH HHS RR-024156NCRR NIH HHS UL1 RR024156NHLBI NIH HHS HL36310NHLBI 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 HC065226NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095169NHLBI 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-65226NHLBI 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 R01 HL036310NIA NIH HHS R01 AG017644NIA NIH HHS R01AG1764406S1PHS HHS 33014PHS HHS HHSN268200960009CWellcome Trust 090532Wellcome Trust 090532/Z/09/ZWHI NIH HHS N01 WH022110WHI NIH HHS N01WH24152WHI NIH HHS N01WH32100-2WHI NIH HHS N01WH32105-6WHI NIH HHS N01WH32108-9WHI NIH HHS N01WH32111-13WHI NIH HHS N01WH32115WHI NIH HHS N01WH32118-32119WHI NIH HHS N01WH32122WHI NIH HHS N01WH42107-26WHI NIH HHS N01WH42129-32WHI NIH HHS N01WH44221
6 · The paper itself

Abstract

aimsTo investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. METHODS AND

resultsWe developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75).

conclusionThe genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.

Indexed as

Case-Control StudiesCholesterol, HDLCoronary Artery DiseaseFemaleGene FrequencyGenotypeGenotyping TechniquesHumansMaleMendelian Randomization AnalysisMiddle AgedPolymorphism, Single NucleotideRisk AssessmentTriglyceridesCholesterol, HDLTriglyceridesAetiologyEpidemiologyHeart diseaseLipidsMendelian randomization

Identifiers

PMID24474739
PMCPMC4344957
OpenAlexW2159738130

What OpenQuestion holds

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LicenceCC BY-NC
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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.