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Sökning: onr:"swepub:oai:lup.lub.lu.se:b2374eac-85fc-43a3-ae93-ef61967a98ed" > Genome-Wide Associa...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00007522naa a2200865 4500
001oai:lup.lub.lu.se:b2374eac-85fc-43a3-ae93-ef61967a98ed
003SwePub
008210120s2021 | |||||||||||000 ||eng|
009oai:DiVA.org:umu-180264
0247 a https://lup.lub.lu.se/record/b2374eac-85fc-43a3-ae93-ef61967a98ed2 URI
0247 a https://doi.org/10.1210/clinem/dgaa6532 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1802642 URI
040 a (SwePub)lud (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Deshmukh, Harshal A.u University of Newcastle upon Tyne,University of Copenhagen4 aut
2451 0a Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity
264 c 2020-09-18
264 1b The Endocrine Society,c 2021
300 a 11 s.
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
653 a beta-cell function
653 a diabetes progression
653 a Glucose intolerance
653 a incretin
653 a mathematical model
653 a Glucose intolerance
7001 a Madsen, Anne Lundageru University of Copenhagen4 aut
7001 a Viñuela, Anau University of Geneva4 aut
7001 a Have, Christian Theilu University of Copenhagen4 aut
7001 a Grarup, Nielsu University of Copenhagen4 aut
7001 a Tura, Andreau Institute of Neuroscience, Università di Padova4 aut
7001 a Mahajan, Anubhau University of Oxford4 aut
7001 a Heggie, Alison J.u University of Newcastle upon Tyne4 aut
7001 a Koivula, Robert W.u 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 Oxford4 aut0 (Swepub:lu)med-rkl
7001 a De Masi, Federicou Technical University of Denmark4 aut
7001 a Tsirigos, Konstantinos K.u Technical University of Denmark4 aut
7001 a Linneberg, Allanu University of Copenhagen,Frederiksberg Hospital4 aut
7001 a Drivsholm, Thomasu Frederiksberg Hospital,University of Copenhagen4 aut
7001 a Pedersen, Olufu University of Copenhagen4 aut
7001 a Sørensen, Thorkild I.A.u University of Copenhagen4 aut
7001 a Astrup, Arneu University of Copenhagen4 aut
7001 a Gjesing, Anette A.P.u University of Copenhagen4 aut
7001 a Pavo, Imreu Eli Lilly Regional Operations G.m.b.H.4 aut
7001 a Wood, Andrew R.u University of Exeter4 aut
7001 a Ruetten, Hartmutu Sanofi-Aventis Deutschland GmbH4 aut
7001 a Jones, Angus G.u University of Exeter4 aut
7001 a Koopman, Anitra D.M.u Amsterdam UMC - Vrije Universiteit Amsterdam4 aut
7001 a Cederberg, Hennau Helsinki University Central Hospital4 aut
7001 a Rutters, Femkeu Amsterdam UMC - Vrije Universiteit Amsterdam4 aut
7001 a Ridderstrale, Martinu Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)endo-mri
7001 a Laakso, Markkuu University of Eastern Finland4 aut
7001 a McCarthy, Mark I.u University of Oxford4 aut
7001 a Frayling, Tim M.u University of Exeter4 aut
7001 a Ferrannini, Eleu CNR Institute of Clinical Physiology (IFC-CNR)4 aut
7001 a Franks, Paul W.u 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 medicin4 aut0 (Swepub:umu)pafr0003
7001 a Pearson, Ewan R.u University of Dundee4 aut0 (Swepub:lu)ew1481pe
7001 a Mari, Andreau Institute of Neuroscience, Università di Padova4 aut
7001 a Hansen, Torbenu University of Copenhagen4 aut
7001 a Walker, Marku University of Newcastle upon Tyne4 aut
7102 a University of Newcastle upon Tyneb University of Copenhagen4 org
7730 t The Journal of clinical endocrinology and metabolismd : The Endocrine Societyg 106:1, s. 80-90q 106:1<80-90x 1945-7197x 0021-972X
8564 u http://dx.doi.org/10.1210/clinem/dgaa653x freey FULLTEXT
8564 u https://academic.oup.com/jcem/article-pdf/106/1/80/36661744/dgaa653.pdf
8564 u https://doi.org/10.1210/clinem/dgaa653y Fulltext
8564 u https://umu.diva-portal.org/smash/get/diva2:1528593/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://lup.lub.lu.se/record/b2374eac-85fc-43a3-ae93-ef61967a98ed
8564 8u https://doi.org/10.1210/clinem/dgaa653
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-180264

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