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A Genome-Wide Assoc...
A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants
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Wood, A. R. (author)
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Jonsson, A. (author)
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Jackson, A. U. (author)
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show more...
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Wang, N. (author)
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van Leewen, N. (author)
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Palmer, N. D. (author)
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Kobes, S. (author)
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Deelen, J. (author)
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Boquete-Vilarino, L. (author)
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Paananen, J. (author)
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Stancakova, A. (author)
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Boomsma, D. I. (author)
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de Geus, E. J. C. (author)
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Eekhoff, E. M. W. (author)
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Fritsche, A. (author)
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Kramer, M. (author)
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Nijpels, G. (author)
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Simonis-Bik, A. (author)
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van Haeften, T. W. (author)
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Mahajan, A. (author)
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Boehnke, M. (author)
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Bergman, R. N. (author)
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Tuomilehto, J. (author)
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Collins, F. S. (author)
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Mohlke, K. L. (author)
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Banasik, K. (author)
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Groves, C. J. (author)
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McCarthy, M. I. (author)
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Pearson, E. R. (author)
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Natali, A. (author)
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Mari, A. (author)
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Buchanan, T. A. (author)
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Taylor, K. D. (author)
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Xiang, A. H. (author)
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Gjesing, A. P. (author)
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Grarup, N. (author)
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Eiberg, H. (author)
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Pedersen, O. (author)
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Chen, Y. D. (author)
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Laakso, M. (author)
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Norris, J. M. (author)
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- Smith, Ulf, 1943 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Wagenknecht, L. E. (author)
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Baier, L. (author)
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Bowden, D. W. (author)
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Hansen, T. (author)
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Walker, M. (author)
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Watanabe, R. M. (author)
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t Hart, L. M. (author)
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Hanson, R. L. (author)
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Frayling, T. M. (author)
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(creator_code:org_t)
- 2017-05-10
- 2017
- English.
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:8, s. 2296-2309
- Related links:
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https://diabetes.dia...
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https://gup.ub.gu.se...
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https://doi.org/10.2...
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Abstract
Subject headings
Close
- Understanding 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 individuals without diabetes from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycemic 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, IGF2BP2, 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 glycemic traits.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- beta-cell function
- glycemic traits
- transcription-factor-7-like-2
- tcf7l2
- genetic architecture
- mexican-americans
- proinsulin levels
- common variants
- iras family
- glucose
- polymorphisms
- lonsky ks
- 1988
- journal of clinical investigation
- v81
- p435
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
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Diabetes
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
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Wood, A. R.
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Jonsson, A.
-
Jackson, A. U.
-
Wang, N.
-
van Leewen, N.
-
Palmer, N. D.
-
show more...
-
Kobes, S.
-
Deelen, J.
-
Boquete-Vilarino ...
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Paananen, J.
-
Stancakova, A.
-
Boomsma, D. I.
-
de Geus, E. J. C ...
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Eekhoff, E. M. W ...
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Fritsche, A.
-
Kramer, M.
-
Nijpels, G.
-
Simonis-Bik, A.
-
van Haeften, T. ...
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Mahajan, A.
-
Boehnke, M.
-
Bergman, R. N.
-
Tuomilehto, J.
-
Collins, F. S.
-
Mohlke, K. L.
-
Banasik, K.
-
Groves, C. J.
-
McCarthy, M. I.
-
Pearson, E. R.
-
Natali, A.
-
Mari, A.
-
Buchanan, T. A.
-
Taylor, K. D.
-
Xiang, A. H.
-
Gjesing, A. P.
-
Grarup, N.
-
Eiberg, H.
-
Pedersen, O.
-
Chen, Y. D.
-
Laakso, M.
-
Norris, J. M.
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Smith, Ulf, 1943
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Wagenknecht, L. ...
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Baier, L.
-
Bowden, D. W.
-
Hansen, T.
-
Walker, M.
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Watanabe, R. M.
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t Hart, L. M.
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Hanson, R. L.
-
Frayling, T. M.
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show less...
- 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 ...
- Articles in the publication
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Diabetes
- By the university
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University of Gothenburg