Evidence map›Paper›PMID 26933753›Full record

ArticleThe New England journal of medicine2016

Inactivating Variants in ANGPTL4 and Risk of Coronary Artery Disease.

Frederick E Dewey, Viktoria Gusarova, Colm O'Dushlaine, Omri Gottesman, Jesus Trejos, Charleen Hunt, Cristopher V Van Hout, Lukas Habegger, David Buckler, Ka-Man V Lai and 16 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 280 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
280citing papers in PubMed, 4 pooled it
44.4field-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

280 citing papers in PubMed, 4 syntheses or guidelines pooled it, 500 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. A Meta-Analysis on the Association BetweenFrontiers in physiology · 2020
    Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Review
  9. Targeting triglycerides for cardiovascular risk reduction.Internal and emergency medicine · 2026
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Observational
  20. Targeting the ANGPTL4/NRP1/ABL1/RAD51 axis reverses cisplatin resistance by impairing DNA damage repair in head and neck cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article

220 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 2 institutions in 1 country.

Frederick E DeweyFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Viktoria GusarovaFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Colm O'DushlaineFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Omri GottesmanFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Jesus TrejosFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Charleen HuntFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Cristopher V Van HoutFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Lukas HabeggerFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
David BucklerFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Ka-Man V LaiFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Joseph B LeaderFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Michael F MurrayFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Marylyn D RitchieFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
H Lester KirchnerFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
David H LedbetterFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
John PennFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Alexander LopezFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Ingrid B BoreckiFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
John D OvertonFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Jeffrey G ReidFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
David J CareyFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Andrew J MurphyFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
George D YancopoulosFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Aris BarasFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Jesper GromadaFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Alan R ShuldinerFrom the Regeneron Genetics Center (F.E.D., C.O., O.G., C.V.V.H., L.H., J.P., A.L., I.B.B., J.D.O., J.G.R., A.J.M., G.D.Y., A.B., J.G., A.R.S.) and Regeneron Pharmaceuticals (V.G., J.T., C.H., D.B., K.-M.V.L., A.J.M., G.D.Y.) - both in Tarrytown, NY; and Geisinger Health System, Danville, PA (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.).
Regeneron (United States) · USGeisinger Health System · US

Funding

Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
NIDDK NIH HHS P30 DK072488
6 · The paper itself

Abstract

backgroundHigher-than-normal levels of circulating triglycerides are a risk factor for ischemic cardiovascular disease. Activation of lipoprotein lipase, an enzyme that is inhibited by angiopoietin-like 4 (ANGPTL4), has been shown to reduce levels of circulating triglycerides.

methodsWe sequenced the exons of ANGPTL4 in samples obtain from 42,930 participants of predominantly European ancestry in the DiscovEHR human genetics study. We performed tests of association between lipid levels and the missense E40K variant (which has been associated with reduced plasma triglyceride levels) and other inactivating mutations. We then tested for associations between coronary artery disease and the E40K variant and other inactivating mutations in 10,552 participants with coronary artery disease and 29,223 controls. We also tested the effect of a human monoclonal antibody against ANGPTL4 on lipid levels in mice and monkeys.

resultsWe identified 1661 heterozygotes and 17 homozygotes for the E40K variant and 75 participants who had 13 other monoallelic inactivating mutations in ANGPTL4. The levels of triglycerides were 13% lower and the levels of high-density lipoprotein (HDL) cholesterol were 7% higher among carriers of the E40K variant than among noncarriers. Carriers of the E40K variant were also significantly less likely than noncarriers to have coronary artery disease (odds ratio, 0.81; 95% confidence interval, 0.70 to 0.92; P=0.002). K40 homozygotes had markedly lower levels of triglycerides and higher levels of HDL cholesterol than did heterozygotes. Carriers of other inactivating mutations also had lower triglyceride levels and higher HDL cholesterol levels and were less likely to have coronary artery disease than were noncarriers. Monoclonal antibody inhibition of Angptl4 in mice and monkeys reduced triglyceride levels.

conclusionsCarriers of E40K and other inactivating mutations in ANGPTL4 had lower levels of triglycerides and a lower risk of coronary artery disease than did noncarriers. The inhibition of Angptl4 in mice and monkeys also resulted in corresponding reductions in these values. (Funded by Regeneron Pharmaceuticals.).

Indexed as

Gene SilencingMutationAgedAngiopoietin-Like Protein 4AngiopoietinsAnimalsCholesterolCoronary Artery DiseaseDisease Models, AnimalFemaleHeterozygoteHumansMacaca mulattaMaleMiceMiddle AgedAngiopoietin-Like Protein 4AngiopoietinsANGPTL4 protein, humanCholesterolTriglycerides

Identifiers

PMID26933753
PMCPMC4900689
OpenAlexW2323589075

What OpenQuestion holds

Textmetadata
LicenceTDM
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.