Skip to Main content Skip to Navigation
Journal articles

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

Robert A. Scott Laura J. Scott Reedik Mägi Letizia Marullo Kyle J. Gaulton Marika Kaakinen Natalia Pervjakova Tune H. Pers Andrew D. Johnson John D. Eicher Anne U. Jackson Teresa Ferreira Yeji Lee Clement Ma Valgerdur Steinthorsdottir Gudmar Thorleifsson Lu Qi Natalie R. van Zuydam Anubha Mahajan Han Chen Peter Almgren Ben F. Voight Harald Grallert Martina Müller-Nurasyid Janina S. Ried Nigel W. Rayner Neil Robertson Lennart C. Karssen Elisabeth M. Leeuwen Sara M. Willems Christian Fuchsberger Phoenix Kwan Tanya M. Teslovich Pritam Chanda Man Li Yingchang Lu Christian Dina 1 Dorothee Thuillier Loic Yengo Longda Jiang Thomas Sparso Hans A. Kestler Himanshu Chheda Lewin Eisele Stefan Gustafsson Mattias Frånberg Rona J. Strawbridge Rafn Benediktsson Astradur B. Hreidarsson Augustine Kong Gunnar Sigurðsson Nicola D. Kerrison Jian'An Luan Liming Liang Thomas Meitinger Michael Roden Barbara Thorand Tõnu Esko Evelin Mihailov Caroline Fox Ching-Ti Liu Denis Rybin Bo Isomaa Valeriya Lyssenko Tiinamaija Tuomi David J. Couper James S. Pankow Niels Grarup Christian T. Have Marit E. Jørgensen Torben Jørgensen Allan Linneberg Marilyn C. Cornelis Rob M. Dam David J. Hunter Peter Kraft Qi Sun Sarah Edkins Katharine R. Owen John R. B. Perry Andrew R. Wood Eleftheria Zeggini Juan Tajes-Fernandes Goncalo R. Abecasis Lori L. Bonnycastle Peter S. Chines Heather M. Stringham Heikki A. Koistinen Leena Kinnunen Bengt Sennblad Thomas W. Mühleisen Markus M. Nöthen Sonali Pechlivanis Damiano Baldassarre Karl Gertow Steve E. Humphries Elena Tremoli Norman Klopp Julia Meyer Gerald Steinbach Roman Wennauer Johan G. Eriksson Satu Mӓnnistö Leena Peltonen Emmi Tikkanen Guillaume Charpentier Elodie Eury Stéphane Lobbens Bruna Gigante Karin Leander Olga Mcleod Erwin P. Bottinger Omri Gottesman Douglas Ruderfer Matthias Blüher Peter Kovacs Anke Tonjes Nisa M. Maruthur Chiara Scapoli Raimund Erbel Karl-Heinz Jöckel Susanne Moebus Ulf Faire Anders Hamsten Michael Stumvoll Panagiotis Deloukas Peter J. Donnelly Timothy M. Frayling Andrew T. Hattersley Samuli Ripatti Veikko Salomaa Nancy L. Pedersen Bernhard O. Boehm Richard N. Bergman Francis S. Collins Karen L. Mohlke Jaakko Tuomilehto Torben Hansen Oluf Pedersen Inês Barroso Lars Lannfelt Erik Ingelsson Lars Lind Cecilia M. Lindgren Stephane Cauchi Philippe Froguel Ruth J. F. Loos Beverley Balkau Heiner Boeing Paul W. Franks Aurelio Barricarte Gurrea Domenico Palli Yvonne T. Schouw David Altshuler Leif C. Groop Claudia Langenberg Nicholas J. Wareham Eric Sijbrands Cornelia M. Duijn Jose C. Florez James B. Meigs Eric Boerwinkle Christian Gieger Konstantin Strauch Andres Metspalu Andrew D. Morris Colin N. A. Palmer Frank B. Hu Unnur Thorsteinsdottir Kari Stefansson Josée Dupuis Andrew P. Morris Michael Boehnke Mark I. Mccarthy Inga Prokopenko Diabetes Genetics Replication Meta-Analysis (diagram) Consortium
Abstract : To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P \textless 5 × 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
Document type :
Journal articles
Complete list of metadatas

https://hal.archives-ouvertes.fr/hal-01832132
Contributor : Stephanie Chatel <>
Submitted on : Friday, July 6, 2018 - 4:01:51 PM
Last modification on : Tuesday, May 26, 2020 - 12:44:05 AM

Links full text

Identifiers

Collections

Citation

Robert A. Scott, Laura J. Scott, Reedik Mägi, Letizia Marullo, Kyle J. Gaulton, et al.. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. Diabetes, 2017, Equipe I, 66 (11), pp.2888--2902. ⟨10.2337/db16-1253⟩. ⟨hal-01832132⟩

Share

Metrics

Record views

248