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The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity

Open access
Dimas, Antigone S., Lagou, Vasiliki, Barker, Adam, Knowles, Joshua W., Mägi, Reedik, Hivert, Marie-France, Benazzo, Andrea, Rybin, Denis, Jackson, Anne U., Stringham, Heather M., Song, Ci, Fischer-Rosinsky, Antje, Boesgaard, Trine Welløv, Grarup, Niels, Abbasi, Fahim A., Assimes, Themistocles L., Hao, Ke, Yang, Xia, Lecoeur, Cécile, Barroso, Inês, Bonnycastle, Lori L., Böttcher, Yvonne, Bumpstead, Suzannah, Chines, Peter S., Erdos, Michael R., Graessler, Jurgen, Kovacs, Peter, Morken, Mario A., Narisu, Narisu, Payne, Felicity, Stancakova, Alena, Swift, Amy J., Tönjes, Anke, Bornstein, Stefan R., Cauchi, Stéphane, Froguel, Philippe, Meyre, David, Schwarz, Peter E.H., Häring, Hans-Ulrich, Smith, Ulf, Boehnke, Michael, Bergman, Richard N., Collins, Francis S., Mohlke, Karen L., Tuomilehto, Jaakko, Quertemous, Thomas, Lind, Lars, Hansen, Torben, Pedersen, Oluf, Walker, Mark, Pfeiffer, Andreas F.H., Spranger, Joachim, Stumvoll, Michael, Meigs, James B., Wareham, Nicholas J., Kuusisto, Johanna, Laakso, Markku, Langenberg, Claudia, Dupuis, Josée, Watanabe, Richard M., Florez, Jose C., Ingelsson, Erik, McCarthy, Mark I., Prokopenko, Inga, on behalf of the MAGIC Investigators·2014·Diabetes

Abstract

Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.

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Authors
Dimas, A. S., Lagou, V., Barker, A., Knowles, J. W., Mägi, R., Hivert, M.-F., Benazzo, A., Rybin, D., Jackson, A. U., Stringham, H. M., Song, C., Fischer-Rosinsky, A., Boesgaard, T. W., Grarup, N., Abbasi, F. A., Assimes, T. L., Hao, K., Yang, X., Lecoeur, C., Barroso, I., Bonnycastle, L. L., Böttcher, Y., Bumpstead, S., Chines, P. S., Erdos, M. R., Graessler, J., Kovacs, P., Morken, M. A., Narisu, N., Payne, F., Stancakova, A., Swift, A. J., Tönjes, A., Bornstein, S. R., Cauchi, S., Froguel, P., Meyre, D., Schwarz, P. E. H., Häring, H.-U., Smith, U., Boehnke, M., Bergman, R. N., Collins, F. S., Mohlke, K. L., Tuomilehto, J., Quertemous, T., Lind, L., Hansen, T., Pedersen, O., Walker, M., Pfeiffer, A. F. H., Spranger, J., Stumvoll, M., Meigs, J. B., Wareham, N. J., Kuusisto, J., Laakso, M., Langenberg, C., Dupuis, J., Watanabe, R. M., Florez, J. C., Ingelsson, E., McCarthy, M. I., Prokopenko, I., & on behalf of the MAGIC Investigators
Venue
Diabetes
Published
2014-05-15
Volume
63
Issue
6
Pages
2158-2171
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2106305501
Cited by
366
References
47
FWCI
21.85
Type
journal article
Language
en
Open access
hybrid

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Dimas, A. S., Lagou, V., Barker, A., Knowles, J. W., Mägi, R., Hivert, M.-F., Benazzo, A., Rybin, D., Jackson, A. U., Stringham, H. M., Song, C., Fischer-Rosinsky, A., Boesgaard, T. W., Grarup, N., Abbasi, F. A., Assimes, T. L., Hao, K., Yang, X., Lecoeur, C., . . . on behalf of the MAGIC Investigators. (2014). Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity. Diabetes. https://doi.org/10.2337/db13-0949

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.