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Integrative genomic...
Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance
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- Lotta, Luca A. (author)
- University of Cambridge
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- Gulati, Pawan (author)
- University of Cambridge
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- Day, Felix R (author)
- University of Cambridge
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- Payne, Felicity (author)
- Wellcome Trust Sanger Institute
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Ongen, Halit (author)
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- van de Bunt, Martijn (author)
- University of Oxford
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Gaulton, Kyle J (author)
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- Eicher, John D. (author)
- National Heart Lung and Blood Institute
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- Sharp, Stephen J. (author)
- University of Cambridge
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- Luan, Jian'an (author)
- University of Cambridge
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- De Lucia Rolfe, Emanuella (author)
- University of Cambridge
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- Stewart, Isobel D. (author)
- University of Cambridge
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- Wheeler, Eleanor (author)
- Wellcome Trust Sanger Institute
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- Willems, Sara M (author)
- University of Cambridge
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- Adams, Claire (author)
- University of Cambridge
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- Yaghootkar, Hanieh (author)
- University of Exeter
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- Sharp, Stephen J. (author)
- University of Cambridge
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- Forouhi, Nita G. (author)
- University of Cambridge
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- Kerrison, Nicola D. (author)
- University of Cambridge
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- Sims, Matt (author)
- University of Cambridge
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- Lucarelli, Debora M E (author)
- University of Cambridge
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- Deloukas, Panos (author)
- University of Cambridge
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- McCarthy, Mark I. (author)
- University of Oxford
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Arriola, Larraitz (author)
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- Balkau, Beverley (author)
- Centre for Research in Epidemiology and Population Health (CESP)
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Barricarte, Aurelio (author)
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- Boeing, Heiner (author)
- German Institute of Human Nutrition
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- Franks, Paul W. (author)
- Umeå University,Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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Gonzalez, Carlos (author)
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Grioni, Sara (author)
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- Kaaks, Rudolf (author)
- German Cancer Research Centre
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- Key, Timothy J (author)
- University of Oxford
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- Navarro, Carmen (author)
- Murcia Regional Health Council
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- Nilsson, Peter M. (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine
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- Overvad, Kim (author)
- Aarhus University,Aalborg University Hospital
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- Palli, Domenico (author)
- Cancer Research and Prevention Institute (ISPO)
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- Panico, Salvatore (author)
- University of Naples Federico II
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- Quirós, J Ramón (author)
- Public Health Directorate
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- Rolandsson, olov (author)
- Umeå universitet,Umeå University,Allmänmedicin
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Sacerdote, Carlotta (author)
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Salamanca-Fernández, Elena (author)
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Slimani, Nadia (author)
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- Tjonneland, Anne (author)
- Danish Cancer Society
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Tumino, Rosario (author)
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Spijkerman, Annemieke M. W. (author)
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van der A, Daphne L. (author)
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van der Schouw, Yvonne T. (author)
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- Riboli, Elio (author)
- Imperial College London
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- Semple, Robert K (author)
- University of Cambridge
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- Stears, Anna (author)
- Addenbrooke's Hospital
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Khaw, Kay-Tee (author)
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Johnson, Andrew D. (author)
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Frayling, Timothy (author)
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Dermitzakis, Emmanouil (author)
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Barroso, Inês (author)
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Wareham, Nicholas J. (author)
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Langenberg, Claudia (author)
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O'Rahilly, Stephen (author)
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Scott, Robert A. (author)
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- 2016-11-14
- 2017
- English 10 s.
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:1, s. 17-26
- Related links:
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http://dx.doi.org/10...
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https://europepmc.or...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
Close
- Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Lotta, Luca A.
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Gulati, Pawan
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Day, Felix R
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Payne, Felicity
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Ongen, Halit
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van de Bunt, Mar ...
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show more...
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Gaulton, Kyle J
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Eicher, John D.
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Sharp, Stephen J ...
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Luan, Jian'an
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De Lucia Rolfe, ...
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Stewart, Isobel ...
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Wheeler, Eleanor
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Willems, Sara M
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Adams, Claire
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Yaghootkar, Hani ...
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Forouhi, Nita G.
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Kerrison, Nicola ...
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Sims, Matt
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Lucarelli, Debor ...
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Deloukas, Panos
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McCarthy, Mark I ...
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Arriola, Larrait ...
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Balkau, Beverley
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Barricarte, Aure ...
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Boeing, Heiner
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Franks, Paul W.
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Gonzalez, Carlos
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Grioni, Sara
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Kaaks, Rudolf
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Key, Timothy J
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Navarro, Carmen
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Nilsson, Peter M ...
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Overvad, Kim
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Palli, Domenico
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Panico, Salvator ...
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Quirós, J Ramón
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Rolandsson, olov
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Sacerdote, Carlo ...
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Salamanca-Fernán ...
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Slimani, Nadia
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Tjonneland, Anne
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Tumino, Rosario
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Spijkerman, Anne ...
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van der A, Daphn ...
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van der Schouw, ...
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Riboli, Elio
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Semple, Robert K
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Stears, Anna
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Khaw, Kay-Tee
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Johnson, Andrew ...
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Frayling, Timoth ...
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Dermitzakis, Emm ...
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Barroso, Inês
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Wareham, Nichola ...
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Langenberg, Clau ...
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O'Rahilly, Steph ...
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Scott, Robert A.
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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 Clinical Medicin ...
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and Endocrinology an ...
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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
- Articles in the publication
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Nature Genetics
- By the university
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Lund University
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Umeå University