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dc.contributor.authorWood, AR
dc.contributor.authorJonsson, A
dc.contributor.authorJackson, AU
dc.contributor.authorWang, N
dc.contributor.authorvan Leewen, N
dc.contributor.authorPalmer, ND
dc.contributor.authorKobes, S
dc.contributor.authorDeelen, J
dc.contributor.authorBoquete-Vilarino, L
dc.contributor.authorPaananen, J
dc.contributor.authorStančáková, A
dc.contributor.authorBoomsma, DI
dc.contributor.authorde Geus, EJ
dc.contributor.authorEekhoff, EM
dc.contributor.authorFritsche, A
dc.contributor.authorKramer, M
dc.contributor.authorNijpels, G
dc.contributor.authorSimonis-Bik, A
dc.contributor.authorvan Haeften, TW
dc.contributor.authorMahajan, A
dc.contributor.authorBoehnke, M
dc.contributor.authorBergman, RN
dc.contributor.authorTuomilehto, J
dc.contributor.authorCollins, FS
dc.contributor.authorMohlke, KL
dc.contributor.authorBanasik, K
dc.contributor.authorGroves, CJ
dc.contributor.authorMcCarthy, MI
dc.contributor.authorPearson, ER
dc.contributor.authorNatali, A
dc.contributor.authorMari, A
dc.contributor.authorBuchanan, TA
dc.contributor.authorTaylor, KD
dc.contributor.authorXiang, AH
dc.contributor.authorGjesing, AP
dc.contributor.authorGrarup, N
dc.contributor.authorEiberg, H
dc.contributor.authorPedersen, O
dc.contributor.authorChen, Y-D
dc.contributor.authorLaakso, M
dc.contributor.authorNorris, JM
dc.contributor.authorSmith, U
dc.contributor.authorWagenknecht, LE
dc.contributor.authorBaier, L
dc.contributor.authorBowden, DW
dc.contributor.authorHansen, T
dc.contributor.authorWalker, M
dc.contributor.authorWatanabe, RM
dc.contributor.author't Hart, LM
dc.contributor.authorHanson, RL
dc.contributor.authorFrayling, TM
dc.date.accessioned2017-05-17T10:05:56Z
dc.date.issued2017-05-10
dc.description.abstractUnderstanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first phase insulin secretion, as measured by intravenous glucose tolerance tests, using up to 5,567 non-diabetic individuals from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycaemic traits and identify new loci. Thirty type 2 diabetes, or fasting glucose raising, alleles were associated with a measure of first phase insulin secretion at P<0.05, and provided new evidence, or the strongest evidence yet, that insulin secretion, intrinsic to the islet cells, is a key mechanism underlying the associations at the HNF1A, IGFBP2, KCNQ1, HNF1B, VPS13C/C2CD4A, FAF1, PTPRD, AP3S2, KCNK16, MAEA, LPP, WFS1 and TMPRSS6 loci. The fasting glucose raising allele near PDX1, a known key insulin transcription factor, was strongly associated with lower first phase insulin secretion but has no evidence for an effect on type 2 diabetes risk. The diabetes risk allele at TCF7L2 was associated with a stronger effect on peak insulin response than on C-peptide-based insulin secretion rate, suggesting a possible additional role in hepatic insulin clearance or insulin processing. In summary, our study provides further insight into the mechanisms by which common genetic variation influences type 2 diabetes risk and glycaemic traits.en_GB
dc.identifier.citationMay 2017, db161452en_GB
dc.identifier.doi10.2337/db16-1452
dc.identifier.otherdb16-1452
dc.identifier.urihttp://hdl.handle.net/10871/27557
dc.language.isoenen_GB
dc.publisherAmerican Diabetes Associationen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/28490609en_GB
dc.rights© 2017 by the American Diabetes Association.en_GB
dc.titleA Genome-Wide Association Study of IVGTT-Based Measures of First Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants.en_GB
dc.typeArticleen_GB
dc.date.available2017-05-17T10:05:56Z
dc.identifier.issn0012-1797
exeter.place-of-publicationUnited Statesen_GB
dc.descriptionPublished onlineen_GB
dc.descriptionJournal Articleen_GB
dc.descriptionThis is the author accepted manuscript. The final version is available from American Diabetes Association via the DOI in this record.en_GB
dc.identifier.eissn1939-327X
dc.identifier.journalDiabetesen_GB


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