Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake

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Williamson, AliceUniversity of Cambridge (author)

Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake

Article/chapterEnglish2023

Publisher, publication year, extent ...

Springer Nature,2023
printrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-505815
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-505815URI
https://doi.org/10.1038/s41588-023-01408-9DOI
https://lup.lub.lu.se/record/6adcc06f-a8d0-4413-9604-f244c2628fdcURI

Supplementary language notes

Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
Blood Glucose
Diabetes Mellitus, Type 2
Genome-Wide Association Study
Glucose
Humans
Insulin
Insulin Resistance
glucose
glucose transporter 4
insulin
adipocyte
ancestry group
Article
body mass
cell culture
controlled study
gene expression
gene identification
genetic variability
genome-wide association study
glucose transport
human
insulin level
insulin resistance
meta analysis (topic)
non insulin dependent diabetes mellitus
transcription regulation
genetics
glucose blood level
metabolism

Added entries (persons, corporate bodies, meetings, titles ...)

Norris, Dougall M (author)
Yin, Xianyong (author)
Broadaway, K Alaine (author)
Moxley, Anne H (author)
Vadlamudi, Swarooparani (author)
Wilson, Emma P (author)
Jackson, Anne U (author)
Ahuja, Vasudha (author)
Andersen, Mette K (author)
Arzumanyan, Zorayr (author)
Bonnycastle, Lori L (author)
Bornstein, Stefan R (author)
Bretschneider, Maxi P (author)
Buchanan, Thomas A (author)
Chang, Yi-Cheng (author)
Chuang, Lee-Ming (author)
Chung, Ren-Hua (author)
Clausen, Tine D (author)
Damm, Peter (author)
Delgado, Graciela E (author)
de Mello, Vanessa D (author)
Dupuis, Josée (author)
Dwivedi, Om P (author)
Erdos, Michael R (author)
Silva, Lilian Fernandes (author)
Frayling, Timothy M (author)
Gieger, Christian (author)
Goodarzi, Mark O (author)
Guo, Xiuqing (author)
Gustafsson, StefanUppsala universitet,Klinisk epidemiologi(Swepub:uu)stegu732 (author)
Hakaste, Liisa (author)
Hammar, UlfUppsala universitet,Molekylär epidemiologi(Swepub:uu)ulfha881 (author)
Hatem, G.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)ga5503ha (author)
Herrmann, Sandra (author)
Højlund, Kurt (author)
Horn, Katrin (author)
Hsueh, Willa A (author)
Hung, Yi-Jen (author)
Hwu, Chii-Min (author)
Jonsson, Anna (author)
Kårhus, Line L (author)
Kleber, Marcus E (author)
Kovacs, Peter (author)
Lakka, Timo A (author)
Lauzon, Marie (author)
Lee, I-Te (author)
Lindgren, Cecilia M (author)
Lindström, Jaana (author)
Linneberg, Allan (author)
Liu, Ching-Ti (author)
Luan, Jian'an (author)
Aly, D.M.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)di3053ma (author)
Mathiesen, Elisabeth (author)
Moissl, Angela P (author)
Morris, Andrew P (author)
Narisu, Narisu (author)
Perakakis, Nikolaos (author)
Peters, Annette (author)
Prasad, R.B.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Helsinki(Swepub:lu)med-rpa (author)
Rodionov, Roman N (author)
Roll, Kathryn (author)
Rundsten, Carsten F (author)
Sarnowski, Chloé (author)
Savonen, Kai (author)
Scholz, Markus (author)
Sharma, Sapna (author)
Stinson, Sara E (author)
Suleman, Sufyan (author)
Tan, Jingyi (author)
Taylor, Kent D (author)
Uusitupa, Matti (author)
Vistisen, Dorte (author)
Witte, Daniel R (author)
Walther, Romy (author)
Wu, Peitao (author)
Xiang, Anny H (author)
Zethelius, BjörnUppsala universitet,Geriatrik(Swepub:uu)bjorzeth (author)
Ahlqvist, E.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)infl-eah (author)
Bergman, Richard N (author)
Chen, Yii-Der Ida (author)
Collins, Francis S (author)
Fall, Tove,1979-Uppsala universitet,Molekylär epidemiologi(Swepub:uu)tovfa878 (author)
Florez, Jose C (author)
Fritsche, Andreas (author)
Grallert, Harald (author)
Groop, L.Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Helsinki(Swepub:lu)endo-lgr (author)
Hansen, Torben (author)
Koistinen, Heikki A (author)
Komulainen, Pirjo (author)
Laakso, Markku (author)
Lind, LarsUppsala universitet,Klinisk epidemiologi(Swepub:uu)larslind (author)
Loeffler, Markus (author)
März, Winfried (author)
Meigs, James BLund University,University Hospital of Tubingen,Massachusetts General Hospital (author)
Raffel, Leslie J (author)
Rauramaa, Rainer (author)
Rotter, Jerome I (author)
Schwarz, Peter E H (author)
Stumvoll, Michael (author)
Sundström, Johan,Professor,1971-Uppsala universitet,Klinisk epidemiologi(Swepub:uu)johasund (author)
Tönjes, Anke (author)
Tuomi, Tiinamaija (author)
Tuomilehto, Jaakko (author)
Wagner, Robert (author)
Barroso, Inês (author)
Walker, Mark (author)
Grarup, Niels (author)
Boehnke, Michael (author)
Wareham, Nicholas J (author)
Mohlke, Karen L (author)
Wheeler, Eleanor (author)
O'Rahilly, Stephen (author)
Fazakerley, Daniel J (author)
Langenberg, ClaudiaQueen Mary University,University of Cambridge,Berlin Institute of Health (BIH),Charité - University Medicine Berlin (author)
University of CambridgeKlinisk epidemiologi (creator_code:org_t)
et al.

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In:Nature Genetics: Springer Nature55:6, s. 973-9831061-40361546-1718

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By the author/editor: Williamson, Alic ...; Norris, Dougall ...; Yin, Xianyong; Broadaway, K Ala ...; Moxley, Anne H; Vadlamudi, Swaro ...; show more...; Wilson, Emma P; Jackson, Anne U; Ahuja, Vasudha; Andersen, Mette ...; Arzumanyan, Zora ...; Bonnycastle, Lor ...; Bornstein, Stefa ...; Bretschneider, M ...; Buchanan, Thomas ...; Chang, Yi-Cheng; Chuang, Lee-Ming; Chung, Ren-Hua; Clausen, Tine D; Damm, Peter; Delgado, Graciel ...; de Mello, Vaness ...; Dupuis, Josée; Dwivedi, Om P; Erdos, Michael R; Silva, Lilian Fe ...; Frayling, Timoth ...; Gieger, Christia ...; Goodarzi, Mark O; Guo, Xiuqing; Gustafsson, Stef ...; Hakaste, Liisa; Hammar, Ulf; Hatem, G.; Herrmann, Sandra; Højlund, Kurt; Horn, Katrin; Hsueh, Willa A; Hung, Yi-Jen; Hwu, Chii-Min; Jonsson, Anna; Kårhus, Line L; Kleber, Marcus E; Kovacs, Peter; Lakka, Timo A; Lauzon, Marie; Lee, I-Te; Lindgren, Cecili ...; Lindström, Jaana; Linneberg, Allan; Liu, Ching-Ti; Luan, Jian'an; Aly, D.M.; Mathiesen, Elisa ...; Moissl, Angela P; Morris, Andrew P; Narisu, Narisu; Perakakis, Nikol ...; Peters, Annette; Prasad, R.B.; Rodionov, Roman ...; Roll, Kathryn; Rundsten, Carste ...; Sarnowski, Chloé; Savonen, Kai; Scholz, Markus; Sharma, Sapna; Stinson, Sara E; Suleman, Sufyan; Tan, Jingyi; Taylor, Kent D; Uusitupa, Matti; Vistisen, Dorte; Witte, Daniel R; Walther, Romy; Wu, Peitao; Xiang, Anny H; Zethelius, Björn; Ahlqvist, E.; Bergman, Richard ...; Chen, Yii-Der Id ...; Collins, Francis ...; Fall, Tove, 1979 ...; Florez, Jose C; Fritsche, Andrea ...; Grallert, Harald; Groop, L.; Hansen, Torben; Koistinen, Heikk ...; Komulainen, Pirj ...; Laakso, Markku; Lind, Lars; Loeffler, Markus; März, Winfried; Meigs, James B; Raffel, Leslie J; Rauramaa, Rainer; Rotter, Jerome I; Schwarz, Peter E ...; Stumvoll, Michae ...; Sundström, Johan ...; Tönjes, Anke; Tuomi, Tiinamaij ...; Tuomilehto, Jaak ...; Wagner, Robert; Barroso, Inês; Walker, Mark; Grarup, Niels; Boehnke, Michael; Wareham, Nichola ...; Mohlke, Karen L; Wheeler, Eleanor; O'Rahilly, Steph ...; Fazakerley, Dani ...; Langenberg, Clau ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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