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Genetic inactivatio...
Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
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- Gusarova, Viktoria (author)
- Regeneron Pharmaceuticals, Inc.
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- O'Dushlaine, Colm (author)
- Regeneron Pharmaceuticals, Inc.
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- Teslovich, Tanya M (author)
- Regeneron Pharmaceuticals, Inc.
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- Benotti, Peter N (author)
- Geisinger Health System
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- Mirshahi, Tooraj (author)
- Geisinger Health System
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- Gottesman, Omri (author)
- Regeneron Pharmaceuticals, Inc.
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- Van Hout, Cristopher V (author)
- Regeneron Pharmaceuticals, Inc.
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- Murray, Michael F (author)
- Geisinger Health System
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- Mahajan, Anubha (author)
- University of Oxford
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- Nielsen, Jonas B (author)
- University of Michigan
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- Fritsche, Lars (author)
- University of Michigan
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- Wulff, Anders Berg (author)
- Copenhagen University Hospital
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Gudbjartsson, Daniel F (author)
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- Sjögren, Marketa (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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- Emdin, Connor A (author)
- Broad Institute
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Scott, Robert A (author)
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- Lee, Wen-Jane (author)
- Tunghai University
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- Small, Aeron (author)
- University of Pennsylvania
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- Kwee, Lydia C (author)
- Duke University
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Dwivedi, Om Prakash (author)
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- Prasad, Rashmi B (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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Bruse, Shannon (author)
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Lopez, Alexander E (author)
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Penn, John (author)
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Marcketta, Anthony (author)
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Leader, Joseph B (author)
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Still, Christopher D (author)
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Kirchner, H Lester (author)
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Mirshahi, Uyenlinh L (author)
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Wardeh, Amr H (author)
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Hartle, Cassandra M (author)
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Habegger, Lukas (author)
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Fetterolf, Samantha N (author)
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Tusie-Luna, Teresa (author)
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- Morris, Andrew P (author)
- University of Tartu
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- Holm, Hilma (author)
- deCODE Genetics
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- Steinthorsdottir, Valgerdur (author)
- deCODE Genetics
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- Sulem, Patrick (author)
- deCODE Genetics
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Thorsteinsdottir, Unnur (author)
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Rotter, Jerome I (author)
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- Chuang, Lee-Ming (author)
- National Taiwan University
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Damrauer, Scott (author)
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- Birtwell, David (author)
- University of Pennsylvania
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Brummett, Chad M (author)
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- Khera, Amit V (author)
- Harvard Medical School
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- Natarajan, Pradeep (author)
- Massachusetts General Hospital
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- Orho-Melander, Marju (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
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- Flannick, Jason (author)
- Broad Institute
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- Lotta, Luca A. (author)
- University of Cambridge
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- Willer, Cristen J (author)
- University of Michigan
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- Holmen, Oddgeir L. (author)
- Norwegian University of Science and Technology
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Ritchie, Marylyn D (author)
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Ledbetter, David H. (author)
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Murphy, Andrew J (author)
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Borecki, Ingrid B (author)
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Reid, Jeffrey G. (author)
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Overton, John D (author)
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- Hansson, Ola (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki
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- Groop, Leif (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki
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- Shah, Svati (author)
- Duke University
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- Kraus, William E (author)
- Duke University
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Rader, Daniel J (author)
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Ida Chen, Yii-Der (author)
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- Hveem, Kristian (author)
- Nord-Trøndelag Health Trust,Norwegian University of Science and Technology
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Wareham, Nicolas J (author)
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- Kathiresan, Sekar (author)
- Massachusetts General Hospital
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- 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
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- Stefansson, Kari (author)
- deCODE Genetics
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- Nordestgaard, Børge G (author)
- University of Copenhagen,Copenhagen University Hospital
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- Tybjaerg-Hansen, Anne (author)
- Copenhagen University Hospital
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Abecasis, Goncalo R. (author)
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- Altshuler, David (author)
- Massachusetts General Hospital,Harvard Medical School,Broad Institute
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- Florez, Jose C. (author)
- Broad Institute,Massachusetts General Hospital,Harvard Medical School
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- Boehnke, Michael (author)
- University of Michigan
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McCarthy, Mark (author)
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Yancopoulos, George D (author)
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Carey, David J. (author)
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Shuldiner, Alan R (author)
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- Baras, Aris (author)
- Regeneron Pharmaceuticals, Inc.
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- Dewey, Frederick E (author)
- Regeneron Pharmaceuticals, Inc.
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- Gromada, Jesper (author)
- Regeneron Pharmaceuticals, Inc.
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Regeneron Pharmaceuticals, Inc Geisinger Health System (creator_code:org_t)
- 2018-06-13
- 2018
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
- Related links:
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http://dx.doi.org/10... (free)
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https://www.nature.c...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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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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- art (subject category)
- ref (subject category)
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Gusarova, Viktor ...
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O'Dushlaine, Col ...
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Teslovich, Tanya ...
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Benotti, Peter N
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Mirshahi, Tooraj
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Gottesman, Omri
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show more...
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Van Hout, Cristo ...
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Murray, Michael ...
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Mahajan, Anubha
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Nielsen, Jonas B
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Fritsche, Lars
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Wulff, Anders Be ...
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Gudbjartsson, Da ...
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Sjögren, Marketa
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Emdin, Connor A
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Scott, Robert A
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Lee, Wen-Jane
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Small, Aeron
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Kwee, Lydia C
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Dwivedi, Om Prak ...
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Prasad, Rashmi B
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Bruse, Shannon
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Lopez, Alexander ...
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Penn, John
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Marcketta, Antho ...
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Leader, Joseph B
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Still, Christoph ...
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Kirchner, H Lest ...
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Mirshahi, Uyenli ...
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Wardeh, Amr H
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Hartle, Cassandr ...
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Habegger, Lukas
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Fetterolf, Saman ...
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Tusie-Luna, Tere ...
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Morris, Andrew P
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Holm, Hilma
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Steinthorsdottir ...
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Sulem, Patrick
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Thorsteinsdottir ...
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Rotter, Jerome I
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Chuang, Lee-Ming
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Damrauer, Scott
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Birtwell, David
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Brummett, Chad M
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Khera, Amit V
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Natarajan, Prade ...
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Orho-Melander, M ...
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Flannick, Jason
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Lotta, Luca A.
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Willer, Cristen ...
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Holmen, Oddgeir ...
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Ritchie, Marylyn ...
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Ledbetter, David ...
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Murphy, Andrew J
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Borecki, Ingrid ...
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Reid, Jeffrey G.
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Overton, John D
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Hansson, Ola
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Groop, Leif
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Shah, Svati
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Kraus, William E
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Rader, Daniel J
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Ida Chen, Yii-De ...
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Hveem, Kristian
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Wareham, Nicolas ...
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Kathiresan, Seka ...
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Melander, Olle
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Stefansson, Kari
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Nordestgaard, Bø ...
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Tybjaerg-Hansen, ...
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Abecasis, Goncal ...
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Altshuler, David
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Florez, Jose C.
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Boehnke, Michael
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McCarthy, Mark
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Yancopoulos, Geo ...
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Carey, David J.
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Shuldiner, Alan ...
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Baras, Aris
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Dewey, Frederick ...
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Gromada, Jesper
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Nature Communica ...
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Lund University