SynthesisJournal of medical genetics2016
Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Journal of medical genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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22citing papers in PubMed, 2 pooled it
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.American journal of epidemiology · 2019Pooled it
- A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.Journal of lipid research · 2017Pooled it
- Genetic analysis of cis-enhancers associated with bone mineral density and periodontitis in the gene SOST.PloS one · 2025Article
- Article
- T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.Annals of medicine · 2024Article
- A Genome-Wide Interaction Study of Erythrocyte ω-3 Polyunsaturated Fatty Acid Species and Memory in the Framingham Heart Study Offspring Cohort.The Journal of nutrition · 2024Article
- An allelic-series rare-variant association test for candidate-gene discovery.American journal of human genetics · 2023Article
- Whole genome sequence analysis of blood lipid levels in >66,000 individuals.Nature communications · 2022Article
- Common and Rare 5'UTR Variants Altering Upstream Open Reading Frames in Cardiovascular Genomics.Frontiers in cardiovascular medicine · 2022Review
- Sclerostin Downregulation Globally by Naturally Occurring Genetic Variants, or Locally in Atherosclerotic Plaques, Does Not Associate With Cardiovascular Events in Humans.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- The Genetic Basis of Hypertriglyceridemia.Current atherosclerosis reports · 2021Review
- GPIHBP1 and ANGPTL4 Utilize Protein Disorder to Orchestrate Order in Plasma Triglyceride Metabolism and Regulate Compartmentalization of LPL Activity.Frontiers in cell and developmental biology · 2021Review
- Genetic architecture of cardiometabolic risks in people living with HIV.BMC medicine · 2020Article
- Angiopoietin-like 4 deficiency upregulates macrophage function through the dysregulation of cell-intrinsic fatty acid metabolism.American journal of cancer research · 2020Article
- Genetic and Epigenetic Fine Mapping of Complex Trait Associated Loci in the Human Liver.American journal of human genetics · 2019Article
- Association of a genetic variant in the angiopoietin-like protein 4 gene with metabolic syndrome.BMC medical genetics · 2019Article
- Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.Nature communications · 2019Article
- A large electronic-health-record-based genome-wide study of serum lipids.Nature genetics · 2018Article
- Article
- Improving power of association tests using multiple sets of imputed genotypes from distributed reference panels.Genetic epidemiology · 2017Article
Corrections and comments
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Authors and funding
100 authors.
Elisabeth M van LeeuwenDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Aniko SaboHuman Genome Sequencing Center, Baylor College of Medicine, Houston, USA.
Joshua C BisDepartment of Medicine, University of Washington, Seattle, USA.
Jennifer E HuffmanMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK The Framingham Heart Study, NHLBI Cardiovascular Epidemiology and Human Genomics Branch, Framingham, USA.
Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, USA.
Albert V SmithIcelandic Heart Association, Kopavogur, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Mary F FeitosaDepartment of Genetics, Washington University School of Medicine, St Louis, USA.
Serkalem DemissieDepartment of Biostatistics, Boston University School of Public Health, Boston, USA.
Peter K JoshiUsher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Qing DuanDepartment of Genetics, University of North Carolina, Chapel Hill, USA.
Jonathan MartenMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Jan B van KlinkenDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Ida SurakkaHuman Genomics Unit, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
Ilja M NolteDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Weihua ZhangDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK Department of Cardiology, Ealing Hospital NHS Trust, Middlesex, UK.
Hamdi MbarekDepartment of Biological Psychology, VU University Amsterdam and EMGO+ Institute for Health and Care Research, Amsterdam, The Netherlands.
Ruifang Li-GaoDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Stella TrompetDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Niek VerweijDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Evangelos EvangelouDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
Leo-Pekka LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.
Bamidele O TayoPublic Health Sciences, Loyola University Chicago Stritch School of Medicine, Maywood, USA.
Joris DeelenDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Peter J van der MostDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Sander W van der LaanLaboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Dan E ArkingMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.
Alanna MorrisonHuman Genetics Center, The University of Texas School of Public Health, Houston, USA.
Abbas DehghanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Oscar H FrancoDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Albert HofmanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Eric J SijbrandsDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Andre G UitterlindenDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Josyf C MychaleckyjCenter for Public Health Genomics, University of Virginia, Charlottesville, USA.
Archie CampbellGeneration Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Lynne J HockingMusculoskeletal Research Programme, Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.
Sandosh PadmanabhanBritish Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Jennifer A BrodyDepartment of Medicine, University of Washington, Seattle, USA.
Kenneth M RiceDepartment of Biostatistics, University of Washington, Seattle, USA.
Charles C WhiteBrigham and Women's Hospital, Boston, USA.
Tamara HarrisLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, USA.
Aaron IsaacsDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Harry CampbellUsher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Leslie A LangeDepartment of Genetics, University of North Carolina, Chapel Hill, USA.
Igor RudanCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Ivana KolcicFaculty of Medicine, University of Split, Split, Croatia.
Pau NavarroMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Tatijana ZemunikFaculty of Medicine, University of Split, Split, Croatia.
Veikko SalomaaDepartment of Health, National Institute for Health and Welfare, Helsinki, Finland.
LifeLines Cohort Study
Angad S KoonerCardiovascular Science, National Heart and Lung Institute, Imperial College London, London, UK.
Jaspal S KoonerDepartment of Cardiology, Ealing Hospital NHS Trust, Middlesex, UK Cardiovascular Science, National Heart and Lung Institute, Imperial College London, London, UK Imperial College Healthcare NHS Trus, Imperial College London, London, UK.
Benjamin LehneDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
William R ScottDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK Department of Cardiology, Ealing Hospital NHS Trust, Middlesex, UK.
Sian-Tsung TanCardiovascular Science, National Heart and Lung Institute, Imperial College London, London, UK.
Eco J de GeusDepartment of Biological Psychology, VU University Amsterdam and EMGO+ Institute for Health and Care Research, Amsterdam, The Netherlands.
Yuri MilaneschiDepartment of Psychiatry, VU University Medical Center Amsterdam/GGZinGeest and EMGO+ Institute for Health and Care Research and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
Brenda W J H PenninxDepartment of Psychiatry, VU University Medical Center Amsterdam/GGZinGeest and EMGO+ Institute for Health and Care Research and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
Gonneke WillemsenDepartment of Biological Psychology, VU University Amsterdam and EMGO+ Institute for Health and Care Research, Amsterdam, The Netherlands.
Renée de MutsertDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Ian FordRobertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
Ron T GansevoortDepartment of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Marcelo P Segura-LepeDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Olli T RaitakariDepartment of Clinical Physiology, Turku University Hospital, Turku, Finland Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Jorma S ViikariDivision of Medicine, Turku University Hospital, Turku, Finland Department of Medicine, University of Turku, Turku, Finland.
Kjell NikusDepartment of Cardiology, Heart Hospital, Tampere University Hospital, Tampere, Finland School of Medicine, University of Tampere, Tampere, Finland.
Terrence ForresterTropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Jamaica.
Colin A McKenzieTropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Jamaica.
Anton J M de CraenDepartment of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Hester M de RuijterLaboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
CHARGE Lipids Working Group
Gerard PasterkampLaboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Albertine J OldehinkelDepartment of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
P Eline SlagboomDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Richard S CooperPublic Health Sciences, Loyola University Chicago Stritch School of Medicine, Maywood, USA.
Mika KähönenDepartment of Clinical Physiology, Tampere University Hospital, Tampere, Finland Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.
Paul ElliottDepartment of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
Pim van der HarstDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands Epidemiology Section, Department of BESC, King Faisal Medical Hospital and Research Centre, Riyadh, Saudi Arabia.
Dorret I BoomsmaDepartment of Biological Psychology, VU University Amsterdam and EMGO+ Institute for Health and Care Research, Amsterdam, The Netherlands.
John C ChambersDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK Department of Cardiology, Ealing Hospital NHS Trust, Middlesex, UK Imperial College Healthcare NHS Trus, Imperial College London, London, UK.
Morris SwertzDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Genomics Coordination Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Samuli RipattiHuman Genomics Unit, Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland Public Health, University of Helsinki, Helsinki, Finland Wellcome Trust Sanger Institute, UK.
Ko Willems van DijkDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Veronique VitartMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Ozren PolasekFaculty of Medicine, University of Split, Split, Croatia.
Caroline HaywardMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
James G WilsonPhysiology and Biophysics, University of Mississippi Medical Center, Jackson, USA.
James F WilsonMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Vilmundur GudnasonIcelandic Heart Association, Kopavogur, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, USA.
Bruce M PsatyDepartment of Medicine, University of Washington, Seattle, USA Department of Epidemiology, University of Washington, Seattle, USA Department of Health Services, University of Washington, Seattle, USA Group Health Cooperative, Group Health Research Institute, Seattle, USA.
Ingrid B BoreckiDepartment of Genetics, Washington University School of Medicine, St Louis, USA.
Eric BoerwinkleHuman Genome Sequencing Center, Baylor College of Medicine, Houston, USA Human Genetics Center, The University of Texas School of Public Health, Houston, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, USA Division of Genomic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, USA Departments of Pediatrics, Medicine, and Human Genetics, UCLA, Los Angeles, USA.
L Adrienne CupplesThe Framingham Heart Study, NHLBI Cardiovascular Epidemiology and Human Genomics Branch, Framingham, USA Department of Genetics, Washington University School of Medicine, St Louis, USA.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Funding
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MGenome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2MEpidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MFHS-SCAN Genome Wide Association Scan for Atherosclerosis Pathway GenesR01HL087700 · NHLBI · WASHINGTON UNIVERSITY · PI PROVINCE, MICHAEL A. · 2006 to 2008
$5.4MProspective meta-analyses of drug-gene interactions: CHARGE GWAS consortiumR01HL103612 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2011 to 2014
$5.4MBritish Heart Foundation SP/04/002Chief Scientist Office CZD/16/6/4Medical Research Council G0601966Medical Research Council G0700931Medical Research Council MC_PC_U127561128Medical Research Council MR/K002414/1Medical Research Council MR/L01341X/1NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001079NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHLBI NIH HHS HHSN268200800007CNHLBI 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 N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI 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 R01 HL059367NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL087700NHLBI NIH HHS R01 HL088215NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL117078NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL080295NIA NIH HHS HHSN271201200022CNIA NIH HHS R01 AG023629NIDDK NIH HHS P30 DK063491Wellcome TrustWellcome Trust 084723/Z/08/Z
Abstract
backgroundSo far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels.
methodsWe used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage.
resultsOur study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene.
conclusionsThis study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.
Indexed as
Angiopoietin-Like Protein 4AngiopoietinsExonsFastingFemaleGenome, HumanGenome-Wide Association StudyGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideAngiopoietin-Like Protein 4AngiopoietinsANGPTL4 protein, humancirculating lipid levelsComplex traitsEpidemiologyGeneticsGenome-wide
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