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Peer-reviewed

GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification

Vasiliki Lagou, Longda Jiang, Anna Ulrich, Liudmila Zudina, Karla Sofia Gutiérrez González, Zhanna Balkhiyarova, Alessia Faggian, Jared G. Maina, Shiqian Chen, Petar V. Todorov, Sodbo Sharapov, Alessia David, Letizia Marullo, Reedik Mägi, Roxana‐Maria Rujan, Emma Ahlqvist, Guðmar Þorleifsson, Ηe Gao, Εvangelos Εvangelou, Beben Benyamin, Robert A. Scott, Aaron Isaacs, Wei Zhao, Sara M. Willems, Toby Johnson, Christian Gieger, Harald Grallert, Christa Meisinger, Martina Müller‐Nurasyid, Rona J. Strawbridge, Anuj Goel, Denis Rybin, Eva Albrecht, Anne Jackson, Heather M. Stringham, Ivan R. Corrêa, Eric Farber‐Eger, Valgerður Steinthórsdóttir, André G. Uitterlinden, Patricia B. Munroe, Morris J. Brown, Julian Schmidberger, Oddgeir L. Holmen, Barbara Thorand, Kristian Hveem, Tom Wilsgaard, Karen L. Mohlke, Zhe Wang, Marcel den Hoed, Aleksey Shmeliov, Marcel den Hoed, Ruth J. F. Loos, Wolfgang Kratzer, Mark Martin Haenle, Wolfgang Köenig, Bernhard O. Boehm, Tricia Tan, Alejandra Tomás, Victoria Salem, Inês Barroso, Jaakko Tuomilehto, Michael Boehnke, Jose C. Florez, Anders Hamsten, Hugh Watkins, Inger Njølstad, H.‐Erich Wichmann, Mark J. Caulfield, Kay‐Tee Khaw, Cornelia M. van Duijn, Albert Hofman, Nicholas J. Wareham, Claudia Langenberg, John B. Whitfield, Nicholas G. Martin, Grant W. Montgomery, Chiara Scapoli, Ioanna Tzoulaki, Paul Elliott, Unnur Þorsteinsdóttir, Kāri Stefánsson, Evan L. Brittain, Mark I. McCarthy, Philippe Froguel, Patrick M. Sexton, Denise Wootten, Leif Groop, Josée Dupuis, James B. Meigs, Giuseppe Deganutti, Ayşe Demirkan, Tune H. Pers, Christopher A. Reynolds, Yurii S. Aulchenko, Marika Kaakinen, Ben Jones, Inga Prokopenko, Cornelia M. van Duijn

Nature Genetics · 2023

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Summary

Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciat

Subject
Dietary patterns & chronic disease
Source type
Peer-reviewed study
System type
Other
DOI
10.1038/s41588-023-01462-3
Catalogue ID
SNmoj1ys4c-9e7xpj
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