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Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes

Gusarova, Viktoria (author)
Regeneron Pharmaceuticals, Inc.
O'Dushlaine, Colm (author)
Regeneron Pharmaceuticals, Inc.
Teslovich, Tanya M (author)
Regeneron Pharmaceuticals, Inc.
show more...
Benotti, Peter N (author)
Geisinger Health System
Mirshahi, Tooraj (author)
Geisinger Health System
Gottesman, Omri (author)
Regeneron Pharmaceuticals, Inc.
Van Hout, Cristopher V (author)
Regeneron Pharmaceuticals, Inc.
Murray, Michael F (author)
Geisinger Health System
Mahajan, Anubha (author)
University of Oxford
Nielsen, Jonas B (author)
University of Michigan
Fritsche, Lars (author)
University of Michigan
Wulff, Anders Berg (author)
Copenhagen University Hospital
Gudbjartsson, Daniel F (author)
Sjögren, Marketa (author)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
Emdin, Connor A (author)
Broad Institute
Scott, Robert A (author)
Lee, Wen-Jane (author)
Tunghai University
Small, Aeron (author)
University of Pennsylvania
Kwee, Lydia C (author)
Duke University
Dwivedi, Om Prakash (author)
Prasad, Rashmi B (author)
Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
Bruse, Shannon (author)
Lopez, Alexander E (author)
Penn, John (author)
Marcketta, Anthony (author)
Leader, Joseph B (author)
Still, Christopher D (author)
Kirchner, H Lester (author)
Mirshahi, Uyenlinh L (author)
Wardeh, Amr H (author)
Hartle, Cassandra M (author)
Habegger, Lukas (author)
Fetterolf, Samantha N (author)
Tusie-Luna, Teresa (author)
Morris, Andrew P (author)
University of Tartu
Holm, Hilma (author)
deCODE Genetics
Steinthorsdottir, Valgerdur (author)
deCODE Genetics
Sulem, Patrick (author)
deCODE Genetics
Thorsteinsdottir, Unnur (author)
Rotter, Jerome I (author)
Chuang, Lee-Ming (author)
National Taiwan University
Damrauer, Scott (author)
Birtwell, David (author)
University of Pennsylvania
Brummett, Chad M (author)
Khera, Amit V (author)
Harvard Medical School
Natarajan, Pradeep (author)
Massachusetts General Hospital
Orho-Melander, Marju (author)
Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
Flannick, Jason (author)
Broad Institute
Lotta, Luca A. (author)
University of Cambridge
Willer, Cristen J (author)
University of Michigan
Holmen, Oddgeir L. (author)
Norwegian University of Science and Technology
Ritchie, Marylyn D (author)
Ledbetter, David H. (author)
Murphy, Andrew J (author)
Borecki, Ingrid B (author)
Reid, Jeffrey G. (author)
Overton, John D (author)
Hansson, Ola (author)
Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki
Groop, Leif (author)
Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki
Shah, Svati (author)
Duke University
Kraus, William E (author)
Duke University
Rader, Daniel J (author)
Ida Chen, Yii-Der (author)
Hveem, Kristian (author)
Norwegian University of Science and Technology,Nord-Trøndelag Health Trust
Wareham, Nicolas J (author)
Kathiresan, Sekar (author)
Massachusetts General Hospital
Melander, Olle (author)
Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Cardiovascular Research - Hypertension,Lund University Research Groups
Stefansson, Kari (author)
deCODE Genetics
Nordestgaard, Børge G (author)
Copenhagen University Hospital,University of Copenhagen
Tybjaerg-Hansen, Anne (author)
Copenhagen University Hospital
Abecasis, Goncalo R. (author)
Altshuler, David (author)
Broad Institute,Massachusetts General Hospital,Harvard Medical School
Florez, Jose C. (author)
Broad Institute,Massachusetts General Hospital,Harvard Medical School
Boehnke, Michael (author)
University of Michigan
McCarthy, Mark (author)
Yancopoulos, George D (author)
Carey, David J. (author)
Shuldiner, Alan R (author)
Baras, Aris (author)
Regeneron Pharmaceuticals, Inc.
Dewey, Frederick E (author)
Regeneron Pharmaceuticals, Inc.
Gromada, Jesper (author)
Regeneron Pharmaceuticals, Inc.
show less...
Regeneron Pharmaceuticals, Inc Geisinger Health System (creator_code:org_t)
2018-06-13
2018
English.
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

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By the author/editor
Gusarova, Viktor ...
O'Dushlaine, Col ...
Teslovich, Tanya ...
Benotti, Peter N
Mirshahi, Tooraj
Gottesman, Omri
show more...
Van Hout, Cristo ...
Murray, Michael ...
Mahajan, Anubha
Nielsen, Jonas B
Fritsche, Lars
Wulff, Anders Be ...
Gudbjartsson, Da ...
Sjögren, Marketa
Emdin, Connor A
Scott, Robert A
Lee, Wen-Jane
Small, Aeron
Kwee, Lydia C
Dwivedi, Om Prak ...
Prasad, Rashmi B
Bruse, Shannon
Lopez, Alexander ...
Penn, John
Marcketta, Antho ...
Leader, Joseph B
Still, Christoph ...
Kirchner, H Lest ...
Mirshahi, Uyenli ...
Wardeh, Amr H
Hartle, Cassandr ...
Habegger, Lukas
Fetterolf, Saman ...
Tusie-Luna, Tere ...
Morris, Andrew P
Holm, Hilma
Steinthorsdottir ...
Sulem, Patrick
Thorsteinsdottir ...
Rotter, Jerome I
Chuang, Lee-Ming
Damrauer, Scott
Birtwell, David
Brummett, Chad M
Khera, Amit V
Natarajan, Prade ...
Orho-Melander, M ...
Flannick, Jason
Lotta, Luca A.
Willer, Cristen ...
Holmen, Oddgeir ...
Ritchie, Marylyn ...
Ledbetter, David ...
Murphy, Andrew J
Borecki, Ingrid ...
Reid, Jeffrey G.
Overton, John D
Hansson, Ola
Groop, Leif
Shah, Svati
Kraus, William E
Rader, Daniel J
Ida Chen, Yii-De ...
Hveem, Kristian
Wareham, Nicolas ...
Kathiresan, Seka ...
Melander, Olle
Stefansson, Kari
Nordestgaard, Bø ...
Tybjaerg-Hansen, ...
Abecasis, Goncal ...
Altshuler, David
Florez, Jose C.
Boehnke, Michael
McCarthy, Mark
Yancopoulos, Geo ...
Carey, David J.
Shuldiner, Alan ...
Baras, Aris
Dewey, Frederick ...
Gromada, Jesper
show less...
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Endocrinology an ...
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Nature Communica ...
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