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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake. / Williamson, Alice; Norris, Dougall M; Yin, Xianyong; Broadaway, K Alaine; Moxley, Anne H; Vadlamudi, Swarooparani; Wilson, Emma P; Jackson, Anne U; Ahuja, Vasudha; Andersen, Mette K; Arzumanyan, Zorayr; Bonnycastle, Lori L; Bornstein, Stefan R; Bretschneider, Maxi P; Buchanan, Thomas A; Chang, Yi-Cheng; Chuang, Lee-Ming; Chung, Ren-Hua; Clausen, Tine D; Damm, Peter; Delgado, Graciela E; de Mello, Vanessa D; Dupuis, Josée; Dwivedi, Om P; Erdos, Michael R; Silva, Lilian Fernandes; Frayling, Timothy M; Gieger, Christian; Goodarzi, Mark O; Guo, Xiuqing; Gustafsson, Stefan; Hakaste, Liisa; Hammar, Ulf; Hatem, Gad; Herrmann, Sandra; Højlund, Kurt; Horn, Katrin; Jonsson, Anna; Kovacs, Peter; Linneberg, Allan; Mathiesen, Elisabeth; Rundsten, Carsten F; Stinson, Sara E; Suleman, Sufyan; Vistisen, Dorte; Witte, Daniel R; Hansen, Torben; Lind, Lars; Schwarz, Peter E H; Grarup, Niels; Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC).
In:
Nature Genetics, Vol. 55, No. 6, 2023, p. 973-983.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Williamson, A, Norris, DM, Yin, X, Broadaway, KA, Moxley, AH, Vadlamudi, S, Wilson, EP, Jackson, AU, Ahuja, V
, Andersen, MK, Arzumanyan, Z, Bonnycastle, LL, Bornstein, SR, Bretschneider, MP, Buchanan, TA, Chang, Y-C, Chuang, L-M, Chung, R-H
, Clausen, TD, Damm, P, Delgado, GE, de Mello, VD, Dupuis, J, Dwivedi, OP, Erdos, MR, Silva, LF, Frayling, TM, Gieger, C, Goodarzi, MO, Guo, X, Gustafsson, S, Hakaste, L, Hammar, U, Hatem, G, Herrmann, S, Højlund, K, Horn, K
, Jonsson, A, Kovacs, P
, Linneberg, A, Mathiesen, E, Rundsten, CF, Stinson, SE, Suleman, S, Vistisen, D, Witte, DR
, Hansen, T, Lind, L
, Schwarz, PEH, Grarup, N & Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) 2023, '
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake',
Nature Genetics, vol. 55, no. 6, pp. 973-983.
https://doi.org/10.1038/s41588-023-01408-9APA
Williamson, A., Norris, D. M., Yin, X., Broadaway, K. A., Moxley, A. H., Vadlamudi, S., Wilson, E. P., Jackson, A. U., Ahuja, V.
, Andersen, M. K., Arzumanyan, Z., Bonnycastle, L. L., Bornstein, S. R., Bretschneider, M. P., Buchanan, T. A., Chang, Y-C., Chuang, L-M., Chung, R-H.
, Clausen, T. D., ... Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) (2023).
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.
Nature Genetics,
55(6), 973-983.
https://doi.org/10.1038/s41588-023-01408-9Vancouver
Williamson A, Norris DM, Yin X, Broadaway KA, Moxley AH, Vadlamudi S et al.
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.
Nature Genetics. 2023;55(6):973-983.
https://doi.org/10.1038/s41588-023-01408-9Author
Williamson, Alice ; Norris, Dougall M ; Yin, Xianyong ; Broadaway, K Alaine ; Moxley, Anne H ; Vadlamudi, Swarooparani ; Wilson, Emma P ; Jackson, Anne U ; Ahuja, Vasudha ; Andersen, Mette K ; Arzumanyan, Zorayr ; Bonnycastle, Lori L ; Bornstein, Stefan R ; Bretschneider, Maxi P ; Buchanan, Thomas A ; Chang, Yi-Cheng ; Chuang, Lee-Ming ; Chung, Ren-Hua ; Clausen, Tine D ; Damm, Peter ; Delgado, Graciela E ; de Mello, Vanessa D ; Dupuis, Josée ; Dwivedi, Om P ; Erdos, Michael R ; Silva, Lilian Fernandes ; Frayling, Timothy M ; Gieger, Christian ; Goodarzi, Mark O ; Guo, Xiuqing ; Gustafsson, Stefan ; Hakaste, Liisa ; Hammar, Ulf ; Hatem, Gad ; Herrmann, Sandra ; Højlund, Kurt ; Horn, Katrin ; Jonsson, Anna ; Kovacs, Peter ; Linneberg, Allan ; Mathiesen, Elisabeth ; Rundsten, Carsten F ; Stinson, Sara E ; Suleman, Sufyan ; Vistisen, Dorte ; Witte, Daniel R ; Hansen, Torben ; Lind, Lars ; Schwarz, Peter E H ; Grarup, Niels ; Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC). / Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake. In: Nature Genetics. 2023 ; Vol. 55, No. 6. pp. 973-983.
Bibtex
@article{6cc53011dbb74818afb87869a4732f45,
title = "Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake",
abstract = "Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10 -8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits. ",
keywords = "Humans, Insulin/genetics, Genome-Wide Association Study, Insulin Resistance/genetics, Diabetes Mellitus, Type 2/genetics, Glucose/metabolism, Blood Glucose/genetics",
author = "Alice Williamson and Norris, {Dougall M} and Xianyong Yin and Broadaway, {K Alaine} and Moxley, {Anne H} and Swarooparani Vadlamudi and Wilson, {Emma P} and Jackson, {Anne U} and Vasudha Ahuja and Andersen, {Mette K} and Zorayr Arzumanyan and Bonnycastle, {Lori L} and Bornstein, {Stefan R} and Bretschneider, {Maxi P} and Buchanan, {Thomas A} and Yi-Cheng Chang and Lee-Ming Chuang and Ren-Hua Chung and Clausen, {Tine D} and Peter Damm and Delgado, {Graciela E} and {de Mello}, {Vanessa D} and Jos{\'e}e Dupuis and Dwivedi, {Om P} and Erdos, {Michael R} and Silva, {Lilian Fernandes} and Frayling, {Timothy M} and Christian Gieger and Goodarzi, {Mark O} and Xiuqing Guo and Stefan Gustafsson and Liisa Hakaste and Ulf Hammar and Gad Hatem and Sandra Herrmann and Kurt H{\o}jlund and Katrin Horn and Anna Jonsson and Peter Kovacs and Allan Linneberg and Elisabeth Mathiesen and Rundsten, {Carsten F} and Stinson, {Sara E} and Sufyan Suleman and Dorte Vistisen and Witte, {Daniel R} and Torben Hansen and Lars Lind and Schwarz, {Peter E H} and Niels Grarup and {Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC)}",
note = "{\textcopyright} 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2023",
doi = "10.1038/s41588-023-01408-9",
language = "English",
volume = "55",
pages = "973--983",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "6",
}
RIS
TY - JOUR
T1 - Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
AU - Williamson, Alice
AU - Norris, Dougall M
AU - Yin, Xianyong
AU - Broadaway, K Alaine
AU - Moxley, Anne H
AU - Vadlamudi, Swarooparani
AU - Wilson, Emma P
AU - Jackson, Anne U
AU - Ahuja, Vasudha
AU - Andersen, Mette K
AU - Arzumanyan, Zorayr
AU - Bonnycastle, Lori L
AU - Bornstein, Stefan R
AU - Bretschneider, Maxi P
AU - Buchanan, Thomas A
AU - Chang, Yi-Cheng
AU - Chuang, Lee-Ming
AU - Chung, Ren-Hua
AU - Clausen, Tine D
AU - Damm, Peter
AU - Delgado, Graciela E
AU - de Mello, Vanessa D
AU - Dupuis, Josée
AU - Dwivedi, Om P
AU - Erdos, Michael R
AU - Silva, Lilian Fernandes
AU - Frayling, Timothy M
AU - Gieger, Christian
AU - Goodarzi, Mark O
AU - Guo, Xiuqing
AU - Gustafsson, Stefan
AU - Hakaste, Liisa
AU - Hammar, Ulf
AU - Hatem, Gad
AU - Herrmann, Sandra
AU - Højlund, Kurt
AU - Horn, Katrin
AU - Jonsson, Anna
AU - Kovacs, Peter
AU - Linneberg, Allan
AU - Mathiesen, Elisabeth
AU - Rundsten, Carsten F
AU - Stinson, Sara E
AU - Suleman, Sufyan
AU - Vistisen, Dorte
AU - Witte, Daniel R
AU - Hansen, Torben
AU - Lind, Lars
AU - Schwarz, Peter E H
AU - Grarup, Niels
AU - Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC)
N1 - © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023
Y1 - 2023
N2 - Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10
-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
AB - Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10
-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
KW - Humans
KW - Insulin/genetics
KW - Genome-Wide Association Study
KW - Insulin Resistance/genetics
KW - Diabetes Mellitus, Type 2/genetics
KW - Glucose/metabolism
KW - Blood Glucose/genetics
U2 - 10.1038/s41588-023-01408-9
DO - 10.1038/s41588-023-01408-9
M3 - Journal article
C2 - 37291194
VL - 55
SP - 973
EP - 983
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 6
ER -
