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Genome-Wide Associa...
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Deshmukh, Harshal A.University of Newcastle upon Tyne,University of Copenhagen
(author)
Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2020-09-18
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The Endocrine Society,2021
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11 s.
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:b2374eac-85fc-43a3-ae93-ef61967a98ed
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https://lup.lub.lu.se/record/b2374eac-85fc-43a3-ae93-ef61967a98edURI
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https://doi.org/10.1210/clinem/dgaa653DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-180264URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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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 and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Madsen, Anne LundagerUniversity of Copenhagen
(author)
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Viñuela, AnaUniversity of Geneva
(author)
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Have, Christian TheilUniversity of Copenhagen
(author)
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Grarup, NielsUniversity of Copenhagen
(author)
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Tura, AndreaInstitute of Neuroscience, Università di Padova
(author)
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Mahajan, AnubhaUniversity of Oxford
(author)
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Heggie, Alison J.University of Newcastle upon Tyne
(author)
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Koivula, Robert W.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(Swepub:lu)med-rkl
(author)
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De Masi, FedericoTechnical University of Denmark
(author)
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Tsirigos, Konstantinos K.Technical University of Denmark
(author)
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Linneberg, AllanUniversity of Copenhagen,Frederiksberg Hospital
(author)
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Drivsholm, ThomasFrederiksberg Hospital,University of Copenhagen
(author)
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Pedersen, OlufUniversity of Copenhagen
(author)
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Sørensen, Thorkild I.A.University of Copenhagen
(author)
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Astrup, ArneUniversity of Copenhagen
(author)
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Gjesing, Anette A.P.University of Copenhagen
(author)
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Pavo, ImreEli Lilly Regional Operations G.m.b.H.
(author)
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Wood, Andrew R.University of Exeter
(author)
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Ruetten, HartmutSanofi-Aventis Deutschland GmbH
(author)
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Jones, Angus G.University of Exeter
(author)
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Koopman, Anitra D.M.Amsterdam UMC - Vrije Universiteit Amsterdam
(author)
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Cederberg, HennaHelsinki University Central Hospital
(author)
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Rutters, FemkeAmsterdam UMC - Vrije Universiteit Amsterdam
(author)
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Ridderstrale, MartinLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-mri
(author)
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Laakso, MarkkuUniversity of Eastern Finland
(author)
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McCarthy, Mark I.University of Oxford
(author)
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Frayling, Tim M.University of Exeter
(author)
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Ferrannini, EleCNR Institute of Clinical Physiology (IFC-CNR)
(author)
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Franks, Paul W.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(Swepub:umu)pafr0003
(author)
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Pearson, Ewan R.University of Dundee(Swepub:lu)ew1481pe
(author)
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Mari, AndreaInstitute of Neuroscience, Università di Padova
(author)
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Hansen, TorbenUniversity of Copenhagen
(author)
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Walker, MarkUniversity of Newcastle upon Tyne
(author)
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University of Newcastle upon TyneUniversity of Copenhagen
(creator_code:org_t)
Related titles
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In:The Journal of clinical endocrinology and metabolism: The Endocrine Society106:1, s. 80-901945-71970021-972X
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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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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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