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Genome-Wide Associa...
Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity
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- Deshmukh, Harshal A. (author)
- University of Newcastle upon Tyne,University of Copenhagen
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- Madsen, Anne Lundager (author)
- University of Copenhagen
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- Viñuela, Ana (author)
- University of Geneva
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- Have, Christian Theil (author)
- University of Copenhagen
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- Grarup, Niels (author)
- University of Copenhagen
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- Tura, Andrea (author)
- Institute of Neuroscience, Università di Padova
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- Mahajan, Anubha (author)
- University of Oxford
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- Heggie, Alison J. (author)
- University of Newcastle upon Tyne
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- Koivula, Robert W. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital,University of Oxford
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- De Masi, Federico (author)
- Technical University of Denmark
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- Tsirigos, Konstantinos K. (author)
- Technical University of Denmark
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- Linneberg, Allan (author)
- University of Copenhagen,Frederiksberg Hospital
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- Drivsholm, Thomas (author)
- Frederiksberg Hospital,University of Copenhagen
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- Pedersen, Oluf (author)
- University of Copenhagen
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- Sørensen, Thorkild I.A. (author)
- University of Copenhagen
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- Astrup, Arne (author)
- University of Copenhagen
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- Gjesing, Anette A.P. (author)
- University of Copenhagen
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- Pavo, Imre (author)
- Eli Lilly Regional Operations G.m.b.H.
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- Wood, Andrew R. (author)
- University of Exeter
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- Ruetten, Hartmut (author)
- Sanofi-Aventis Deutschland GmbH
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- Jones, Angus G. (author)
- University of Exeter
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- Koopman, Anitra D.M. (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Cederberg, Henna (author)
- Helsinki University Central Hospital
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- Rutters, Femke (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Ridderstrale, Martin (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Laakso, Markku (author)
- University of Eastern Finland
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- McCarthy, Mark I. (author)
- University of Oxford
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- Frayling, Tim M. (author)
- University of Exeter
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- Ferrannini, Ele (author)
- CNR Institute of Clinical Physiology (IFC-CNR)
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- Franks, Paul W. (author)
- Umeå universitet,Umeå University,Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, UK; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Lund University, Sweden; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts,Harvard University,Skåne University Hospital,Avdelningen för medicin
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- Pearson, Ewan R. (author)
- University of Dundee
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- Mari, Andrea (author)
- Institute of Neuroscience, Università di Padova
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- Hansen, Torben (author)
- University of Copenhagen
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- Walker, Mark (author)
- University of Newcastle upon Tyne
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(creator_code:org_t)
- 2020-09-18
- 2021
- English 11 s.
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:1, s. 80-90
- Related links:
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http://dx.doi.org/10... (free)
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https://academic.oup...
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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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
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- CONTEXT: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. OBJECTIVE: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. DESIGN: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. RESULTS: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10-9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10-9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. CONCLUSION: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.
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)
Keyword
- beta-cell function
- diabetes progression
- Glucose intolerance
- incretin
- mathematical model
- Glucose intolerance
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Deshmukh, Harsha ...
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Madsen, Anne Lun ...
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Viñuela, Ana
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Have, Christian ...
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Grarup, Niels
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Tura, Andrea
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show more...
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Mahajan, Anubha
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Heggie, Alison J ...
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Koivula, Robert ...
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De Masi, Federic ...
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Tsirigos, Konsta ...
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Linneberg, Allan
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Drivsholm, Thoma ...
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Pedersen, Oluf
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Sørensen, Thorki ...
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Astrup, Arne
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Gjesing, Anette ...
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Pavo, Imre
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Wood, Andrew R.
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Ruetten, Hartmut
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Jones, Angus G.
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Koopman, Anitra ...
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Cederberg, Henna
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Rutters, Femke
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Ridderstrale, Ma ...
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Laakso, Markku
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McCarthy, Mark I ...
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Frayling, Tim M.
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Ferrannini, Ele
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Franks, Paul W.
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Pearson, Ewan R.
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Mari, Andrea
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Hansen, Torben
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Walker, Mark
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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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The Journal of c ...
- By the university
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Lund University
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Umeå University