ArticleNature communications2018
Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
13.5field-weighted citation impact, top 1% of its field
What it found
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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.
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.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Cardiac Metabolomic Alterations in Diabetes: Interplay with Lipoprotein Lipase-A Systematic Review.International journal of molecular sciences · 2025Pooled it
- DNA methylation changes and improved sleep quality in adults with obstructive sleep apnea and diabetes.BMJ open diabetes research & care · 2019Trial
- The Angiopoietin-like Protein (ANGPTL) Axis in Dyslipidemia: Mechanisms, Cardiovascular Risk, and Emerging Therapies.Current atherosclerosis reports · 2026Review
- Drug targets for lipid modification and risk of type 2 diabetes: a cis-Mendelian randomization study.Cardiovascular diabetology · 2026Article
- Unraveling the physiological impact of ANGPTL8 loss-of-function variants in humans.Scientific reports · 2026Article
- Genomics of drug target prioritization for complex diseases.Nature reviews. Genetics · 2026Review
- Activated Human Pancreatic Stellate Cells SignatureCommunication in Type 1 Diabetes.Research square · 2026Article
- Kidney angiopoietin-like protein 4 regulates fibrotic responses in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- Hepatokines and polycystic ovary syndrome: investigating the connection between the hepato-ovarian axis and disorders in glycolipid metabolism in PCOS: a narrative review.Frontiers in endocrinology · 2026Review
- Increased Serum Angiopoietin-like Peptide 4 in Impaired Glucose Tolerance and Diabetes Subjects with or Without Hepatic Steatosis.Journal of clinical medicine · 2025Article
- Time-Restricted Eating, ANGPTL4, and Reduction in Residual Cardiovascular Risk.Journal of clinical medicine · 2025Article
- Distinct endothelial gene responses to acute exercise in skeletal muscle.American journal of physiology. Endocrinology and metabolism · 2025Article
- Obesity genetic association prospective cohort utilizing single center real-world evidence data.Medicine · 2025Article
- Genetic architecture of plasma metabolome in 254,825 individuals.Nature communications · 2025Article
- Proteogenomic and observational evidence implicate ANGPTL4 as a potential therapeutic target for colorectal cancer prevention.Journal of the National Cancer Institute · 2025Article
- Obesity induces phenotypic switching of gastric smooth muscle cells through the activation of the PPARD/PDK4/ANGPTL4 pathway.Journal of biomedical science · 2025Article
- Cardiac endothelial cells and cardiomyocytes alter their communication properties in diabetic mice.Biological research · 2025Article
- Evaluating the Cardiometabolic Efficacy and Safety of Lipoprotein Lipase Pathway Targets in Combination With Approved Lipid-Lowering Targets: A Drug Target Mendelian Randomization Study.Circulation. Genomic and precision medicine · 2025Article
- Protein Drug Targets for Abdominal Aortic Aneurysm and Proteomic Associations Between Modifiable Risk Factors and Abdominal Aortic Aneurysm.Journal of the American Heart Association · 2025Article
- The combination of circulating levels of ANGPTL, omentin-1, leptin and cytokines is associated with polycystic ovary syndrome in different BMI groups.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2025Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
81 authors at 20 institutions in 10 countries.
Viktoria GusarovaRegeneron Pharmaceuticals, Tarrytown, 10591, NY, USA.
Colm O'DushlaineRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Tanya M TeslovichRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Peter N BenottiGeisinger, Danville, 17822, PA, USA.
Tooraj MirshahiGeisinger, Danville, 17822, PA, USA.ORCID http://orcid.org/0000-0002-0754-3820
Omri GottesmanRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Cristopher V Van HoutRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Michael F MurrayGeisinger, Danville, 17822, PA, USA.
Anubha MahajanWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.ORCID http://orcid.org/0000-0001-5585-3420
Jonas B NielsenDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, University of Michigan, Ann Arbor, 48109, MI, USA.ORCID http://orcid.org/0000-0002-6654-2852
Lars FritscheDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.ORCID http://orcid.org/0000-0002-2110-1690
Anders Berg WulffDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2100, Denmark.
Daniel F GudbjartssondeCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland.ORCID http://orcid.org/0000-0002-5222-9857
Marketa SjögrenDepartment of Clinical Sciences, Malmö, Lund University, Malmö, 221, Sweden.
Connor A EmdinProgram in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, USA.ORCID http://orcid.org/0000-0002-2385-8259
Robert A ScottMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
Wen-Jane LeeDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, 40705, Taiwan.
Aeron SmallDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, PA, USA.
Lydia C KweeDivision of Cardiology, Department of Medicine; Molecular Physiology Institute, School of Medicine, Duke University, Durham, 27710, NC, USA.
Om Prakash DwivediFinnish Institute of Molecular Medicine (FIMM), Helsinki University, Helsinki, 00170, Finland.
Rashmi B PrasadDepartment of Clinical Sciences, Clinical Research Centre, Lund University, Malmö, 221, Sweden.ORCID http://orcid.org/0000-0002-4400-6741
Shannon BruseRegeneron Genetics Center, Tarrytown, 10591, NY, USA.ORCID http://orcid.org/0000-0002-3037-6266
Alexander E LopezRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
John PennRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Anthony MarckettaRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Joseph B LeaderGeisinger, Danville, 17822, PA, USA.ORCID http://orcid.org/0000-0002-4101-5423
Christopher D StillGeisinger, Danville, 17822, PA, USA.
H Lester KirchnerGeisinger, Danville, 17822, PA, USA.
Uyenlinh L MirshahiGeisinger, Danville, 17822, PA, USA.
Amr H WardehGeisinger, Danville, 17822, PA, USA.
Cassandra M HartleGeisinger, Danville, 17822, PA, USA.
Lukas HabeggerRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Samantha N FetterolfGeisinger, Danville, 17822, PA, USA.
Teresa Tusie-LunaInstituto de Investigaciones Biomédicas, UNAM, Coyoacán, 04510, Mexico City, Mexico.
Andrew P MorrisWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Hilma HolmdeCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland.
Valgerdur SteinthorsdottirdeCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland.
Patrick SulemdeCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland.ORCID http://orcid.org/0000-0001-7123-6123
Unnur ThorsteinsdottirdeCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, 90502, CA, USA.
Lee-Ming ChuangDivision of Endocrinology & Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 10617, Taiwan.
Scott DamrauerDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, PA, USA.
David BirtwellDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, PA, USA.
Chad M BrummettDepartment of Anesthesiology, University of Michigan, Ann Arbor, 48109, MI, USA.
Amit V KheraProgram in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, USA.
Pradeep NatarajanProgram in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, USA.
Marju Orho-MelanderDepartment of Clinical Sciences, Malmö, Lund University, Malmö, 221, Sweden.
Jason FlannickProgram in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, USA.
Luca A LottaMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
Cristen J WillerDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, University of Michigan, Ann Arbor, 48109, MI, USA.ORCID http://orcid.org/0000-0001-5645-4966
Oddgeir L HolmenHUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, 7601, Norway.
Marylyn D RitchieGeisinger, Danville, 17822, PA, USA.ORCID http://orcid.org/0000-0002-1208-1720
David H LedbetterGeisinger, Danville, 17822, PA, USA.ORCID http://orcid.org/0000-0001-8934-4210
Andrew J MurphyRegeneron Pharmaceuticals, Tarrytown, 10591, NY, USA.ORCID http://orcid.org/0000-0003-4152-4081
Ingrid B BoreckiRegeneron Genetics Center, Tarrytown, 10591, NY, USA.ORCID http://orcid.org/0000-0002-8657-7964
Jeffrey G ReidRegeneron Genetics Center, Tarrytown, 10591, NY, USA.ORCID http://orcid.org/0000-0001-8645-4713
John D OvertonRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Ola HanssonFinnish Institute of Molecular Medicine (FIMM), Helsinki University, Helsinki, 00170, Finland.ORCID http://orcid.org/0000-0002-7394-7639
Leif GroopFinnish Institute of Molecular Medicine (FIMM), Helsinki University, Helsinki, 00170, Finland.ORCID http://orcid.org/0000-0002-0187-3263
Svati H ShahDivision of Cardiology, Department of Medicine; Molecular Physiology Institute, School of Medicine, Duke University, Durham, 27710, NC, USA.
William E KrausDivision of Cardiology, Department of Medicine; Molecular Physiology Institute, School of Medicine, Duke University, Durham, 27710, NC, USA.
Daniel J RaderDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, PA, USA.
Yii-Der I ChenInstitute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, 90502, CA, USA.
Kristian HveemHUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, 7601, Norway.
Nicholas J WarehamMRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
Sekar KathiresanCenter for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, MA, USA.ORCID http://orcid.org/0000-0002-6724-032X
Olle MelanderDepartment of Clinical Sciences, Malmö, Lund University, Malmö, 221, Sweden.
Kari StefanssondeCODE Genetics/Amgen, Inc., Reykjavik, 101, Iceland.
Børge G NordestgaardThe Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, 2730, Denmark.ORCID http://orcid.org/0000-0002-1954-7220
Anne Tybjærg-HansenDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2100, Denmark.
Goncalo R AbecasisDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
David AltshulerProgram in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, USA.
Jose C FlorezDiabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, 02115, MA, USA.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
Mark I McCarthyWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.ORCID http://orcid.org/0000-0002-4393-0510
George D YancopoulosRegeneron Pharmaceuticals, Tarrytown, 10591, NY, USA.
David J CareyGeisinger, Danville, 17822, PA, USA.
Alan R ShuldinerRegeneron Genetics Center, Tarrytown, 10591, NY, USA.
Aris BarasRegeneron Genetics Center, Tarrytown, 10591, NY, USA. aris.baras@regeneron.com.
Frederick E DeweyRegeneron Genetics Center, Tarrytown, 10591, NY, USA. rickdewey@gmail.com.
Jesper GromadaRegeneron Pharmaceuticals, Tarrytown, 10591, NY, USA. jesper.gromada@regeneron.com.
Regeneron (United States) · USGeisinger Medical Center · USBroad Institute · USdeCODE Genetics (Iceland) · ISUniversity of Michigan · USCentre for Human Genetics · GBDuke University · USLund University · SEMalmö University · SEUniversity of Cambridge · GBUniversity of Pennsylvania · USNorwegian University of Science and Technology · NOThe Lundquist Institute · USUniversity of Copenhagen · DKCopenhagen University Hospital · DKHarvard University · USInstitute for Molecular Medicine Finland · FIInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXNational Taiwan University · TWPhiladelphia VA Medical Center · US
Funding
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLIAM H HERMAN · 2013 to 2026
$24.3MIdentifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6MUsing genetics to discover mechanisms of myocardial infarctionR01HL109946 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YUQING Eugene CHEN, Ida Liisa Surakka · 2011 to 2026
$8.9MHarvard Clinical and Translational Science CenterKL2TR001100 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$8.5MUsing Genetics to Inform Mechanism of Cardiovascular DiseaseR35HL135824 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WILLER, CRISTEN J · 2017 to 2022
$5.4MUnderstanding modifiers of mendelian mutation penetrance using familial hypercholesterolemia as a modelK08HL140203 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NATARAJAN, PRADEEP · 2018 to 2019
$343kMedical Research Council MC_UU_12015/1NCATS NIH HHS KL2 TR001100NHLBI NIH HHS K08 HL140203NHLBI NIH HHS R01 HL109946NHLBI NIH HHS R35 HL135824NIDDK NIH HHS P30 DK020572NIDDK NIH HHS U01 DK062370
Abstract
Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10
Indexed as
Amino Acid SubstitutionAngiopoietin-Like Protein 4AnimalsBlood GlucoseCase-Control StudiesDiabetes Mellitus, Type 2Exome SequencingFemaleGene SilencingGenetic Association StudiesGenetic VariationHeterozygoteHomeostasisHumansInsulin ResistanceLipoprotein LipaseAngiopoietin-Like Protein 4ANGPTL4 protein, humanAngptl4 protein, mouseBlood GlucoseLipoprotein Lipase
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