Nature Communications (Jun 2018)
Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- Viktoria Gusarova,
- Colm O’Dushlaine,
- Tanya M. Teslovich,
- Peter N. Benotti,
- Tooraj Mirshahi,
- Omri Gottesman,
- Cristopher V. Van Hout,
- Michael F. Murray,
- Anubha Mahajan,
- Jonas B. Nielsen,
- Lars Fritsche,
- Anders Berg Wulff,
- Daniel F. Gudbjartsson,
- Marketa Sjögren,
- Connor A. Emdin,
- Robert A. Scott,
- Wen-Jane Lee,
- Aeron Small,
- Lydia C. Kwee,
- Om Prakash Dwivedi,
- Rashmi B. Prasad,
- Shannon Bruse,
- Alexander E. Lopez,
- John Penn,
- Anthony Marcketta,
- Joseph B. Leader,
- Christopher D. Still,
- H. Lester Kirchner,
- Uyenlinh L. Mirshahi,
- Amr H. Wardeh,
- Cassandra M. Hartle,
- Lukas Habegger,
- Samantha N. Fetterolf,
- Teresa Tusie-Luna,
- Andrew P. Morris,
- Hilma Holm,
- Valgerdur Steinthorsdottir,
- Patrick Sulem,
- Unnur Thorsteinsdottir,
- Jerome I. Rotter,
- Lee-Ming Chuang,
- Scott Damrauer,
- David Birtwell,
- Chad M. Brummett,
- Amit V. Khera,
- Pradeep Natarajan,
- Marju Orho-Melander,
- Jason Flannick,
- Luca A. Lotta,
- Cristen J. Willer,
- Oddgeir L. Holmen,
- Marylyn D. Ritchie,
- David H. Ledbetter,
- Andrew J. Murphy,
- Ingrid B. Borecki,
- Jeffrey G. Reid,
- John D. Overton,
- Ola Hansson,
- Leif Groop,
- Svati H. Shah,
- William E. Kraus,
- Daniel J. Rader,
- Yii-Der I. Chen,
- Kristian Hveem,
- Nicholas J. Wareham,
- Sekar Kathiresan,
- Olle Melander,
- Kari Stefansson,
- Børge G. Nordestgaard,
- Anne Tybjærg-Hansen,
- Goncalo R. Abecasis,
- David Altshuler,
- Jose C. Florez,
- Michael Boehnke,
- Mark I. McCarthy,
- George D. Yancopoulos,
- David J. Carey,
- Alan R. Shuldiner,
- Aris Baras,
- Frederick E. Dewey,
- Jesper Gromada
Affiliations
- Viktoria Gusarova
- Regeneron Pharmaceuticals
- Colm O’Dushlaine
- Regeneron Genetics Center
- Tanya M. Teslovich
- Regeneron Genetics Center
- Peter N. Benotti
- Geisinger
- Tooraj Mirshahi
- Geisinger
- Omri Gottesman
- Regeneron Genetics Center
- Cristopher V. Van Hout
- Regeneron Genetics Center
- Michael F. Murray
- Geisinger
- Anubha Mahajan
- Wellcome Centre for Human Genetics, University of Oxford
- Jonas B. Nielsen
- Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, University of Michigan
- Lars Fritsche
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan
- Anders Berg Wulff
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital
- Daniel F. Gudbjartsson
- deCODE Genetics/Amgen, Inc.
- Marketa Sjögren
- Department of Clinical Sciences, Malmö, Lund University
- Connor A. Emdin
- Program in Medical and Population Genetics, Broad Institute
- Robert A. Scott
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke’s Hospital
- Wen-Jane Lee
- Department of Medical Research, Taichung Veterans General Hospital
- Aeron Small
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania
- Lydia C. Kwee
- Division of Cardiology, Department of Medicine; Molecular Physiology Institute, School of Medicine, Duke University
- Om Prakash Dwivedi
- Finnish Institute of Molecular Medicine (FIMM), Helsinki University
- Rashmi B. Prasad
- Department of Clinical Sciences, Clinical Research Centre, Lund University
- Shannon Bruse
- Regeneron Genetics Center
- Alexander E. Lopez
- Regeneron Genetics Center
- John Penn
- Regeneron Genetics Center
- Anthony Marcketta
- Regeneron Genetics Center
- Joseph B. Leader
- Geisinger
- Christopher D. Still
- Geisinger
- H. Lester Kirchner
- Geisinger
- Uyenlinh L. Mirshahi
- Geisinger
- Amr H. Wardeh
- Geisinger
- Cassandra M. Hartle
- Geisinger
- Lukas Habegger
- Regeneron Genetics Center
- Samantha N. Fetterolf
- Geisinger
- Teresa Tusie-Luna
- Instituto de Investigaciones Biomédicas, UNAM, Coyoacán
- Andrew P. Morris
- Wellcome Centre for Human Genetics, University of Oxford
- Hilma Holm
- deCODE Genetics/Amgen, Inc.
- Valgerdur Steinthorsdottir
- deCODE Genetics/Amgen, Inc.
- Patrick Sulem
- deCODE Genetics/Amgen, Inc.
- Unnur Thorsteinsdottir
- deCODE Genetics/Amgen, Inc.
- Jerome I. Rotter
- Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center
- Lee-Ming Chuang
- Division of Endocrinology & Metabolism, Department of Internal Medicine, National Taiwan University Hospital
- Scott Damrauer
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania
- David Birtwell
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania
- Chad M. Brummett
- Department of Anesthesiology, University of Michigan
- Amit V. Khera
- Program in Medical and Population Genetics, Broad Institute
- Pradeep Natarajan
- Program in Medical and Population Genetics, Broad Institute
- Marju Orho-Melander
- Department of Clinical Sciences, Malmö, Lund University
- Jason Flannick
- Program in Medical and Population Genetics, Broad Institute
- Luca A. Lotta
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke’s Hospital
- Cristen J. Willer
- Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, University of Michigan
- Oddgeir L. Holmen
- HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology
- Marylyn D. Ritchie
- Geisinger
- David H. Ledbetter
- Geisinger
- Andrew J. Murphy
- Regeneron Pharmaceuticals
- Ingrid B. Borecki
- Regeneron Genetics Center
- Jeffrey G. Reid
- Regeneron Genetics Center
- John D. Overton
- Regeneron Genetics Center
- Ola Hansson
- Finnish Institute of Molecular Medicine (FIMM), Helsinki University
- Leif Groop
- Finnish Institute of Molecular Medicine (FIMM), Helsinki University
- Svati H. Shah
- Division of Cardiology, Department of Medicine; Molecular Physiology Institute, School of Medicine, Duke University
- William E. Kraus
- Division of Cardiology, Department of Medicine; Molecular Physiology Institute, School of Medicine, Duke University
- Daniel J. Rader
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania
- Yii-Der I. Chen
- Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center
- Kristian Hveem
- HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology
- Nicholas J. Wareham
- MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Addenbrooke’s Hospital
- Sekar Kathiresan
- Center for Human Genetic Research, Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School
- Olle Melander
- Department of Clinical Sciences, Malmö, Lund University
- Kari Stefansson
- deCODE Genetics/Amgen, Inc.
- Børge G. Nordestgaard
- The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital
- Anne Tybjærg-Hansen
- Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital
- Goncalo R. Abecasis
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan
- David Altshuler
- Program in Medical and Population Genetics, Broad Institute
- Jose C. Florez
- Diabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital
- Michael Boehnke
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan
- Mark I. McCarthy
- Wellcome Centre for Human Genetics, University of Oxford
- George D. Yancopoulos
- Regeneron Pharmaceuticals
- David J. Carey
- Geisinger
- Alan R. Shuldiner
- Regeneron Genetics Center
- Aris Baras
- Regeneron Genetics Center
- Frederick E. Dewey
- Regeneron Genetics Center
- Jesper Gromada
- Regeneron Pharmaceuticals
- DOI
- https://doi.org/10.1038/s41467-018-04611-z
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 11
Abstract
Genetic variation in ANGPTL4 is associated with lipid traits. Here, the authors find that predicted loss-of-function variants in ANGPTL4 are associated with glucose homeostasis and reduced risk of type 2 diabetes and that Angptl4 −/− mice on a high-fat diet show improved insulin sensitivity.
