@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",
}