Evidence map›Paper›PMID 31664920›Full record

ArticleBMC cardiovascular disorders2019

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

Amand F Schmidt, Michael V Holmes, David Preiss, Daniel I Swerdlow, Spiros Denaxas, Ghazaleh Fatemifar, Rupert Faraway, Chris Finan, Dennis Valentine, Zammy Fairhurst-Hunter and 158 more

Open access · goldFull text readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cardiovascular disorders, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 3% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Open heart · 2025
    Observational
  5. Review
  6. Article
  7. Causal inference in health and disease: a review of the principles and applications of Mendelian randomization.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. PCSK9 Inhibition and Risk of Diabetes: Should We Worry?Current atherosclerosis reports · 2022
    Review
  14. Article
  15. Review
  16. Common and RareInternational journal of molecular sciences · 2022
    Article
  17. Review
  18. Review
  19. Target Discovery for Drug Development Using Mendelian Randomization.Methods in molecular biology (Clifton, N.J.) · 2022
    Review
  20. Archives of medical science : AMS · 2021
    Article
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

168 authors at 20 institutions in 20 countries.

Amand F SchmidtInstitute of Cardiovascular Science, University College London, 222 Euston Road, London, NW1 2DA, UK. amand.schmidt@ucl.ac.uk.ORCID 0000-0003-1327-0424
Michael V HolmesMedical Research Council Population Health Research Unit, Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
David PreissMedical Research Council Population Health Research Unit, Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Daniel I SwerdlowInstitute of Cardiovascular Science, University College London, 222 Euston Road, London, NW1 2DA, UK.
Spiros DenaxasUCL's BHF Research Accelerator Centre, London, UK.
Ghazaleh FatemifarUCL's BHF Research Accelerator Centre, London, UK.
Rupert FarawayInstitute of Cardiovascular Science, University College London, 222 Euston Road, London, NW1 2DA, UK.
Chris FinanInstitute of Cardiovascular Science, University College London, 222 Euston Road, London, NW1 2DA, UK.
Dennis ValentineUCL's BHF Research Accelerator Centre, London, UK.
Zammy Fairhurst-HunterClinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LF, UK.
Fernando Pires HartwigPostgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
Bernardo Lessa HortaPostgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
Elina HypponenCentre for Population Health Research, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia.
Christine PowerPopulation, Policy and Practice, UCL GOS Institute of Child Health, London, UK.
Max MoldovanSouth Australian Health and Medical Research Institute, Adelaide, Australia.
Erik van IperenDurrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, The Netherlands.
Kees HovinghDepartment of vascular medicine, Academic Medical Center Amsterdam, Amsterdam, the Netherlands.
Ilja DemuthCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Lipid Clinic at the Interdisciplinary Metabolism Center, Berlin, Germany.
Kristina NormanInstitute of Nutritional Science, University of Potsdam, 14558, Nuthetal, Germany.
Elisabeth Steinhagen-ThiessenCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Lipid Clinic at the Interdisciplinary Metabolism Center, Berlin, Germany.
Juri DemuthE.CA Economics GmbH, Berlin, Germany.
Lars BertramLübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.
Christina M LillGenetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.
Stefan CoassinInstitute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, 6020, Innsbruck, Austria.
Johann WilleitDepartment of Neurology, Medical University Innsbruck, Innsbruck, Austria.
Stefan KiechlDepartment of Neurology, Medical University Innsbruck, Innsbruck, Austria.
Karin WilleitDepartment of Neurology, Medical University Innsbruck, Innsbruck, Austria.
Dan MasonBradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK.
John WrightBradford Institute for Health Research, Bradford Royal Infirmary, Bradford, UK.
Richard MorrisDepartment Primary Care & Population Health, University College London, London, UK.
Goya WanametheeDepartment Primary Care & Population Health, University College London, London, UK.
Peter WhincupPopulation Health Research Institute, St George's, University of London, London, UK.
Yoav Ben-ShlomoPopulation Health Sciences, University of Bristol, Bristol, UK.
Stela McLachlanCentre for Population Health Sciences, The Usher Institute, University of Edinburgh, Edinburgh, UK.
Jackie F PriceCentre for Population Health Sciences, The Usher Institute, University of Edinburgh, Edinburgh, UK.
Mika KivimakiDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, London, UK.
Catherine WelchDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, London, UK.
Adelaida Sanchez-GalvezDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, London, UK.
Pedro Marques-VidalDepartment of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Andrew NicolaidesDepartment of Vascular Surgery, Imperial College, London, United Kingdom.
Andrie G PanayiotouCyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus.
N Charlotte Onland-MoretJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Yvonne T van der SchouwJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Giuseppe MatulloItalian Institute for Genomic Medicine (IIGM), Turin, Italy.
Giovanni FioritoItalian Institute for Genomic Medicine (IIGM), Turin, Italy.
Simonetta GuarreraItalian Institute for Genomic Medicine (IIGM), Turin, Italy.
Carlotta SacerdoteUnit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
Nicholas J WarehamMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK.
Claudia LangenbergMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK.
Robert A ScottMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK.
Jian'an LuanMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK.
Martin BobakDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, London, UK.
Sofia MalyutinaNovosibirsk State Medical University, Novosibirsk, Russian Federation.
Andrzej PająkDepartment of Epidemiology and Population Studies, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland.
Ruzena KubinovaNational Institute of Public Health, Prague, Czech Republic.
Abdonas TamosiunasLithuanian University of Health Sciences, Kaunas, Lithuania.
Hynek PikhartDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, London, UK.
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Allan LinnebergDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Tine JessCenter for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, The Capital Region of Denmark, Denmark.
Jackie CooperCentre for Cardiovascular Genetics, Department of Medicine, University College London, London, UK.
Steve E HumphriesCentre for Cardiovascular Genetics, Department of Medicine, University College London, London, UK.
Murray BrilliantCenter for Human Genetics, Marshfield Clinic Research Institute, Marshfield, USA.
Terrie KitchnerCenter for Human Genetics, Marshfield Clinic Research Institute, Marshfield, USA.
Hakon HakonarsonChildren's Hospital of Philadelphia, Philadelphia, USA.
David S CarrellKaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Catherine A McCartyUniversity of Minnesota, Minneapolis, USA.
Kirchner H LesterGeisinger, Danville, USA.
Eric B LarsonKaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
David R CrosslinDepartment of Biomedical Informatics and Medical Education University of Washington Seattle, Seattle, WA, USA.
Mariza de AndradeMayo Clinic, Rochester, USA.
Dan M RodenDepartment of Medicine, Department of Pharmacology, Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA.
Joshua C DennyVanderbilt University, Nashville, USA.
Cara CartyWHI, Seattle, USA.
Stephen HancockUniversity of Newcastle, Newcastle, NSW, Australia.
John AttiaUniversity of Newcastle, Newcastle, NSW, Australia.
Elizabeth HollidayUniversity of Newcastle, Newcastle, NSW, Australia.
Rodney ScottUniversity of Newcastle, Newcastle, NSW, Australia.
Peter SchofieldHunter New England Local Health District, Newcastle, NSW, Australia.
Martin O'DonnellPopulation Health Research Institute, Hamilton, Ontario, Canada.
Salim YusufPopulation Health Research Institute, Hamilton, Ontario, Canada.
Michael ChongPopulation Health Research Institute, Hamilton, Ontario, Canada.
Guillaume ParePopulation Health Research Institute, Hamilton, Ontario, Canada.
Pim van der HarstDurrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, The Netherlands.
M Abdullah SaidDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Ruben N EppingaDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Niek VerweijDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Lifelines Cohort authors
Tim ChristenDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
D O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
ICBP Consortium
Stefan GustafssonDepartment of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
Lars LindDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Erik IngelssonDepartment of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
Raha PazokiDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Oscar FrancoDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Albert HofmanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Andre UitterlindenDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Abbas DehghanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Sebastian BaumeisterInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Marcus DörrDZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
Markus M LerchDepartment of Internal Medicine A, University Medicine Greifswald, Greifswald, Germany.
Uwe VölkerDZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Joey WardInstitute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8RZ, Scotland, UK.
Jill P PellInstitute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8RZ, Scotland, UK.
Tom MeadeDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Ingrid E ChristophersenThe Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway.
Anke H Maitland-van der ZeeDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Ekaterina V BaranovaRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Robin YoungRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Ian FordRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Archie CampbellInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Sandosh PadmanabhanInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Michiel L BotsCyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus.
Diederick E GrobbeeCyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus.
Philippe FroguelCNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, 59000, Lille, France.
Dorothée ThuillierCNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, 59000, Lille, France.
Ronan RousselINSERM, U-1138, Centre de Recherche des Cordeliers, Paris, France.
Amélie BonnefondCNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, 59000, Lille, France.
Bertrand Carioul'institut du Thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
Melissa SmartInstitute for Social and Economic Research, University of Essex, Essex, UK.
Yanchun BaoWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, England.
Meena KumariBoston University School of Medicine, Boston, MA, USA.
Anubha MahajanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, England.
Jemma C HopewellClinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LF, UK.
Sudha SeshadriBoston University School of Medicine, Boston, MA, USA.
METASTROKE Consortium of the ISGC
Caroline DaleUniversity College London, Farr Institute of Health Informatics, London, UK.
Rui Providencia E CostaUniversity College London, Farr Institute of Health Informatics, London, UK.
Paul M RidkerHarvard Medical School Center for Cardiovascular Disease Prevention Brigham and Women's Hospital, Boston, USA.
Daniel I ChasmanHarvard Medical School Center for Cardiovascular Disease Prevention Brigham and Women's Hospital, Boston, USA.
Alex P ReinerUWash, Seattle, USA.
Marylyn D RitchiePenn State, State College, USA.
Leslie A LangeUniversity of Colorado Denver, Denver, USA.
Alex J CornishDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Sara E DobbinsDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Kari HemminkiDiv. Molecular Genetic Epidemiology German Cancer Research Center, Im Neuenheimer Feld 580, 69120, Heidelberg, Germany.
Ben KinnersleyDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Marc SansonThe Institut du Cerveau et de la Moelle épinière - ICM, Paris, France.
Karim LabrecheThe Institut du Cerveau et de la Moelle épinière - ICM, Paris, France.
Matthias SimonDepartment of Neurosurgery, Bethel Clinic, Kantensiek 11, 33617, Bielefeld, Germany.
Melissa BondyDivision of Hematology-Oncology, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, 77030, USA.
Philip LawDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Helen SpeedyDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
James AllanNorthern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
Ni LiDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Molly WentDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Niels WeinholdMyeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA.
Gareth MorganMyeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA.
Pieter SonneveldDepartment of Hematology, Erasmus MC Cancer Institute, 3075 EA, Rotterdam, the Netherlands.
Björn NilssonHematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, SE-221 84, Lund, Sweden.
Hartmut GoldschmidtUniversity Clinic Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
Amit SudDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Andreas EngertDepartment of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
Markus HanssonHematology Clinic, Skåne University Hospital, Skåne, Sweden.
Harry HemingwayUCL's BHF Research Accelerator Centre, London, UK.
Folkert W AsselbergsInstitute of Cardiovascular Science, University College London, 222 Euston Road, London, NW1 2DA, UK.
Riyaz S PatelInstitute of Cardiovascular Science, University College London, 222 Euston Road, London, NW1 2DA, UK.
Brendan J KeatingUPenn, Philadelphia, USA.
Naveed SattarInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
Richard HoulstonDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
Juan P CasasMassachusetts Veterans Epidemiology and Research Information Center (MAVERIC) Veterans Affairs Boston Healthcare System, Boston, USA.
Aroon D HingoraniInstitute of Cardiovascular Science, University College London, 222 Euston Road, London, NW1 2DA, UK.
Institute of Cancer Research · GBUniversity College London · GBUniversitätsmedizin Greifswald · DEUniversity of Cambridge · GBCentre National de la Recherche Scientifique · FRInter-University Accelerator Centre · INPopulation Health Research Institute · CAUniversity Medical Center Groningen · NLUniversity of Copenhagen · DKBrigham and Women's Hospital · USCyprus University of Technology · CYErasmus MC · NLInnsbruck Medical University · ATUniversity of Glasgow · GBUniversity of Oxford · GBUppsala University · SEUtrecht University · NLCentre for Human Genetics · GBItalian institute for Genomic Medicine · ITLund University · SE

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Collaborative GWAS of Dementia, AD and related MRI and Cognitive EndophenotypesR01AG033193 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2016
$4.4M
Toward the Neural Basis of Episodic MemoryF32MH065841 · NIMH · BOSTON UNIVERSITY · PI HOWARD, MARC W · 2002 to 2002
$18k
Arthritis Research UKBritish Heart Foundation AA/18/6/24223British Heart Foundation FS/14/76/30933British Heart Foundation FS/18/23/33512British Heart Foundation PG/13/66/30442British Heart Foundation PG/18/50/33837British Heart Foundation PG/18/5033837British Heart Foundation RE/13/1/30181British Heart Foundation RG/10/12/28456British Heart Foundation RG/13/16/30528British Heart Foundation SP/13/6/30554Cancer Research UK 14136Cancer Research UK C1298/A8362Chief Scientist OfficeDepartment of HealthMedical Research Council 503480Medical Research Council G0401527Medical Research Council G0500300Medical Research Council G1000143Medical Research Council K013351Medical Research Council MC_UU_12015/1Medical Research Council MR/K006584/1Medical Research Council MR/N003284/1Medical Research Council MR/R024227/1Medical Research Council MR/S011676/1Medical Research Council R024227NHLBI NIH HHS R01 HL105756NIA NIH HHS R01 AG033193NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886NIMH NIH HHS F32 MH065841Wellcome Trust 064947/Z/01/ZWellcome Trust 081081/Z/06/ZWellcome Trust 082604/2/07/Z
6 · The paper itself

Abstract

backgroundWe characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.

methodsPublished and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration.

resultsThe PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable.

conclusionsGenetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

Indexed as

PCSK9 InhibitorsPolymorphism, Single NucleotideAnticholesteremic AgentsBiomarkersBrain IschemiaCholesterol, LDLDown-RegulationDyslipidemiasGenome-Wide Association StudyHumansMyocardial InfarctionProprotein Convertase 9Randomized Controlled Trials as TopicRisk AssessmentRisk FactorsSerine Proteinase InhibitorsAnticholesteremic AgentsBiomarkersCholesterol, LDLPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9Serine Proteinase InhibitorsGenetic association studiesLDL-cholesterolMendelian randomisationPhenome-wide association scan

Identifiers

PMID31664920
PMCPMC6820948
OpenAlexW2974509005

What OpenQuestion holds

Textfull text, public
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.