Evidence map›Paper›PMID 27908689›Full record

ArticleThe lancet. Diabetes & endocrinology2017

PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study.

Amand F Schmidt, Daniel I Swerdlow, Michael V Holmes, Riyaz S Patel, Zammy Fairhurst-Hunter, Donald M Lyall, Fernando Pires Hartwig, Bernardo Lessa Horta, Elina Hyppönen, Christine Power and 125 more

2 registry-linked trialsOpen access · hybridFull text read
PubMed Full text at PMC Publisher
In one paragraph

Article in The lancet. Diabetes & endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 181 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed, 9 pooled it
53.0field-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.

NCT03394859 completednot on this map

Electronic Medical Records and Genomics (eMERGE) Phase III

TypeobservationalSponsorVanderbilt University Medical CenterRan2015 to 2020Enrolled25,380ConditionsCardiac Disease, Cancer, Hypercholesterolemia, Diabetes
NCT04485871 narecruitingnot on this mapstarted 2019, after this paper: background citation

White Adipose Tissue LDL Receptors and Omega-3 as Modulators of the Risk for Type 2 Diabetes in Subjects With Normal Plasma LDL Cholesterol

TypeinterventionalSponsorInstitut de Recherches Cliniques de MontrealRan2019 to 2027Enrolled48ConditionsType 2 Diabetes, Inflammation, Insulin Sensitivity/Resistance, Fatty Acids, Omega-3ArmsOmega-3 fatty acids
3 · Its place in the literature

Who cites it

181 citing papers in PubMed, 9 syntheses or guidelines pooled it, 384 citations in OpenAlex.

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  9. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.The Cochrane database of systematic reviews · 2017 · on this map
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  14. Large-Scale Phenome-Wide Association Study ofCirculation. Genomic and precision medicine · 2018
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121 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

135 authors at 20 institutions in 19 countries.

Amand F SchmidtInstitute of Cardiovascular Science, University College London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK. Electronic address: amand.schmidt@ucl.ac.uk.
Daniel I SwerdlowInstitute of Cardiovascular Science, University College London, UK; Department of Medicine, Imperial College London, London, UK.
Michael V HolmesClinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK; Medical Research Council Population Health Research Unit at the University of Oxford, University of Oxford, Oxford, UK.
Riyaz S PatelInstitute of Cardiovascular Science, University College London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK; The Barts Heart Centre, St Bartholomew's Hospital, London, UK.
Zammy Fairhurst-HunterWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Donald M LyallInstitute of Health & Wellbeing, University of Glasgow, Glasgow, 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 HyppönenCentre for Population Health Research, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia; Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, UK; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
Christine PowerPopulation, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, UK.
Max MoldovanSchool of Health Sciences, University of South Australia, Adelaide, SA, Australia; South Australian Health and Medical Research Institute-EMBL Australia, Adelaide, SA, Australia.
Erik van IperenDurrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center Amsterdam, Netherlands.
G Kees HovinghDepartment of Vascular Medicine, Academic Medical Center Amsterdam, Netherlands.
Ilja DemuthCharité Research Group on Geriatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany; Institute of Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Kristina NormanCharité Research Group on Geriatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Elisabeth Steinhagen-ThiessenCharité Research Group on Geriatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Juri DemuthE.CA Economics GmbH, Berlin, Germany.
Lars BertramNeuroepidemiology and Ageing Research Unit, Imperial College London, London, UK; Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
Tian LiuMax Planck Institute for Human Development, Berlin, Germany; Max Planck Institute for Molecular Genetics, Berlin, Germany.
Stefan CoassinDivision of Genetic Epidemiology Innsbruck, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Johann WilleitDepartment of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Stefan KiechlDepartment of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Karin WilleitDepartment of Neurology, Medical University of 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 MorrisSchool of Social and Community Medicine, University of Bristol, Bristol, UK.
Goya WanametheeDepartment of Primary Care & Population Health, University College London, UK.
Peter WhincupPopulation Health Research Institute, St George's, University of London, London, UK.
Yoav Ben-ShlomoSchool of Social and Community Medicine, University of Bristol, Bristol, UK.
Stela McLachlanCentre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Jackie F PriceCentre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Mika KivimakiDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
Catherine WelchDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
Adelaida Sanchez-GalvezDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
Pedro Marques-VidalInternal Medicine Unit, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Andrew NicolaidesDepartment of Vascular Surgery, Imperial College London, London, UK; Department of Surgery, Nicosia Medical School, University of Nicosia, Nicosia, Cyprus.
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, Netherlands.
Yvonne T van der SchouwJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
Giuseppe MatulloHuman Genetics Foundation, HuGeF, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy.
Giovanni FioritoHuman Genetics Foundation, HuGeF, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy.
Simonetta GuarreraHuman Genetics Foundation, HuGeF, Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy.
Carlotta SacerdoteCancer Epidemiology Unit, San Giovanni Battista Hospital, Turin, Italy; Centre for Oncology Prevention, CPO Piemonte, Turin, Italy.
Nicholas J WarehamMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Claudia LangenbergMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Robert ScottMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Jian'an LuanMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Martin BobakDepartment of Epidemiology and Public Health, UCL Institute of Epidemiology and Health Care, University College London, UK.
Sofia MalyutinaNovosibirsk State Medical University, Novosibirsk, Russia; Institute of Internal and Preventive Medicine, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia.
Andrzej PająkJagiellonian University Collegium Medicum, Krakow, 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, UK.
Lise Lotte Nystrup HusemoenResearch Centre for Prevention and Health, Capital Region of Denmark, Denmark.
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 LinnebergResearch Centre for Prevention and Health, Capital Region of Denmark, Denmark; Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kenneth Starup SimonsenResearch Centre for Prevention and Health, Capital Region of Denmark, Denmark.
Jackie CooperCentre for Cardiovascular Genetics, University College London, UK.
Steve E HumphriesCentre for Cardiovascular Genetics, University College London, UK.
Murray BrilliantCenter for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
Terrie KitchnerCenter for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
Hakon HakonarsonChildren's Hospital of Philadelphia, Philadelphia, PA, USA.
David S CarrellGroup Health Research Institute in Seattle, WA, USA.
Catherine A McCartyEssentia Institute of Rural Health, Duluth, MN, USA.
H Lester KirchnerCenter for Health Research, Geisinger Clinic, Danville, PA, USA.
Eric B LarsonGroup Health Research Institute, Seattle, WA, USA.
David R CrosslinGroup Health Research Institute, Seattle, WA, USA.
Mariza de AndradeDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
Dan M RodenDepartments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Joshua C DennyDepartment of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA.
Cara CartyGeorge Washington University, Washington, DC, USA.
Stephen HancockUniversity of Newcastle, Newcastle, NSW, Australia.
John AttiaUniversity of Newcastle, Newcastle, NSW, Australia.
Elizabeth HollidayUniversity of Newcastle, Newcastle, NSW, Australia.
Martin O'DonnellPopulation Health Research Institute, Hamilton, ON, Canada.
Salim YusufPopulation Health Research Institute, Hamilton, ON, Canada.
Michael ChongPopulation Health Research Institute, Hamilton, ON, Canada.
Guillaume ParePopulation Health Research Institute, Hamilton, ON, Canada.
Pim van der HarstDurrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, Netherlands; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
M Abdullah SaidDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Ruben N EppingaDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Niek VerweijDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Harold SniederDepartment of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
LifeLines Cohort study group
Tim ChristenDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
Stefan GustafssonMolecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Lars LindMolecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Erik IngelssonMolecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Raha PazokiDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
Oscar FrancoDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
Albert HofmanDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
Andre UitterlindenDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
Abbas DehghanFaculty of Medicine, and Department of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
Sebastian BaumeisterInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
Marcus DörrDepartment of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
Markus M LerchDepartment of Medicine A, University Medicine Greifswald, Greifswald, Germany.
Uwe VölkerInterfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
Joey WardInstitute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
Jill P PellInstitute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
Daniel J SmithInstitute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
Tom MeadeDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Anke H Maitland-van der ZeeDepartment of Respiratory Medicine, Academic Medical Center Amsterdam, Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
Ekaterina V BaranovaDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.
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, UK.
Michiel L BotsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
Diederick E GrobbeeJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
Philippe FroguelDepartment of Genomics of Common Disease, Imperial College London, London, UK; CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
Dorothée ThuillierCNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
Beverley BalkauRenal and Cardiovascular Epidemiology, Centre de Recherche en Epidémiologie et Santé des Populations (CESP), INSERM U1018, Villejuif, France.
Amélie BonnefondDepartment of Genomics of Common Disease, Imperial College London, London, UK; CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
Bertrand CariouI'institut du Thorax, INSERM, CNRS, University of Nantes, CHU de Nantes, Nantes, France.
Melissa SmartInstitute for Social and Economic Research, University of Essex, Colchester, Essex, UK.
Yanchun BaoInstitute for Social and Economic Research, University of Essex, Colchester, Essex, UK.
Meena KumariInstitute for Social and Economic Research, University of Essex, Colchester, Essex, UK.
Anubha MahajanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Paul M RidkerHarvard Medical School Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA, USA.
Daniel I ChasmanHarvard Medical School Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA, USA.
Alex P ReinerDepartment of Epidemiology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
Leslie A LangeAnschutz Medical Campus, University of Colorado Denver, Denver, CO, USA.
Marylyn D RitchieBiomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA; Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA.
Folkert W AsselbergsInstitute of Cardiovascular Science, University College London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK; Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands.
Juan-Pablo CasasFarr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK.
Brendan J KeatingDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
David PreissClinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK; Medical Research Council Population Health Research Unit at the University of Oxford, University of Oxford, Oxford, UK.
Aroon D HingoraniInstitute of Cardiovascular Science, University College London, UK; Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, UK.
UCLEB consortium
Naveed SattarInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. Electronic address: naveed.sattar@glasgow.ac.uk.
University College London · GBUniversity of Glasgow · GBUniversitätsmedizin Greifswald · DEErasmus MC · NLUniversity Medical Center Groningen · NLUniversity Medical Center Utrecht · NLCentre National de la Recherche Scientifique · FRInnsbruck Medical University · ATPopulation Health Research Institute · CAUniversity of Cambridge · GBUniversity of Copenhagen · DKCharité - Universitätsmedizin Berlin · DEFarr Institute · GBItalian institute for Genomic Medicine · ITKaiser Permanente Washington Health Research Institute · USUniversity of Essex · GBUniversity of Newcastle Australia · AUUppsala University · SEAmsterdam UMC Location University of Amsterdam · NLBradford Royal Infirmary · GB

Funding

The Electronic Medical Records and Genomics (eMERGE) Network Phase III Coordinating Center (U01)U01HG008701 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PETERSON, JOSEPH F. · 2015 to 2019
$7.1M
The Women's Health Study: Infrastructure Support for Continued Cohort Follow-upUM1CA182913 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 2014 to 2018
$4.0M
Causal associations of circulating biomarkers with cardiovascular diseaseR01HL135313 · NHLBI · STANFORD UNIVERSITY · PI INGELSSON, ERIK · 2017 to 2019
$1.6M
British Heart Foundation FS/14/76/30933British Heart Foundation PG/12/71/29684British Heart Foundation PG/13/66/30442British Heart Foundation RG/08/008/25291British Heart Foundation RG/08/013/25942British Heart Foundation RG/10/12/28456British Heart Foundation RG/13/16/30528Chief Scientist Office CZD/16/6/4Medical Research Council G0802432Medical Research Council G1001799Medical Research Council MC_PC_13042Medical Research Council MC_QA137853Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12015/1Medical Research Council MR/K006584/1Medical Research Council MR/K006665/1Medical Research Council MR/K013351/1Medical Research Council MR/N01104X/1Medical Research Council MR/N01104X/2NCI NIH HHS UM1 CA182913NHGRI NIH HHS U01 HG008701NHLBI NIH HHS R01 HL135313
6 · The paper itself

Abstract

backgroundStatin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.

methodsIn this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA

findingsData were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA

interpretationPCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins.

fundingBritish Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.

Indexed as

Blood GlucoseCase-Control StudiesCholesterol, LDLCohort StudiesDiabetes Mellitus, Type 2Genetic Predisposition to DiseaseGenetic VariationHumansMendelian Randomization AnalysisProprotein Convertase 9Randomized Controlled Trials as TopicBlood GlucoseCholesterol, LDLPCSK9 protein, humanProprotein Convertase 9

Identifiers

PMID27908689
PMCPMC5266795
OpenAlexW2559592043

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Registered trials

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.