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

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Authors
Scott, Robert A
Scott, Laura J
Mägi, Reedik
Marullo, Letizia
Gaulton, Kyle J
Kaakinen, Marika
Pervjakova, Natalia
Pers, Tune H
Johnson, Andrew D
Eicher, John D
Jackson, Anne U
Deloukas, Panagiotis
Donnelly, Peter J
Frayling, Timothy M
Hattersley, Andrew T
Ripatti, Samuli
Ma, Clement
Salomaa, Veikko
Robertson, Neil
Pedersen, Nancy L
Boehm, Bernhard O
Yengo, Loic
Bergman, Richard N
Collins, Francis S
Mohlke, Karen L
Tuomilehto, Jaakko
Hansen, Torben
Pedersen, Oluf
Barroso, Inês
Steinthorsdottir, Valgerdur
Karssen, Lennart C
Lannfelt, Lars
Jiang, Longda
Ingelsson, Erik
Lind, Lars
Lindgren, Cecilia M
Cauchi, Stephane
Froguel, Philippe
Loos, Ruth J F
Balkau, Beverley
Boeing, Heiner
Franks, Paul W
van Leeuwen, Elisabeth M
Sparso, Thomas
Thorleifsson, Gudmar
Barricarte Gurrea, Aurelio
Palli, Domenico
van der Schouw, Yvonne T
Altshuler, David
Groop, Leif C
Langenberg, Claudia
Wareham, Nicholas J
Sijbrands, Eric
van Duijn, Cornelia M
Kestler, Hans A
Willems, Sara M
Florez, Jose C
Qi, Lu
Meigs, James B
Boerwinkle, Eric
Gieger, Christian
Strauch, Konstantin
Metspalu, Andres
Morris, Andrew D
Palmer, Colin N A
Chheda, Himanshu
Hu, Frank B
Fuchsberger, Christian
Thorsteinsdottir, Unnur
Stefansson, Kari
Van Zuydam, Natalie R
Dupuis, Josée
Morris, Andrew P
Boehnke, Michael
McCarthy, Mark I
Prokopenko, Inga
Eisele, Lewin
Mahajan, Anubha
Chen, Han
Kwan, Phoenix
Almgren, Peter
Voight, Ben F
Grallert, Harald
Müller-Nurasyid, Martina
Ried, Janina S
Teslovich, Tanya M
Chanda, Pritam
Gustafsson, Stefan
Li, Man
Wennauer, Roman
Lu, Yingchang
Dina, Christian
Thuillier, Dorothee
Eriksson, Johan G
Frånberg, Mattias
Strawbridge, Rona J
Ruderfer, Douglas
Benediktsson, Rafn
Hreidarsson, Astradur B
Kong, Augustine
Sigurðsson, Gunnar
Kerrison, Nicola D
Luan, Jian'an
Liang, Liming
Meitinger, Thomas
Mӓnnistö, Satu
Roden, Michael
Blüher, Matthias
Thorand, Barbara
Esko, Tõnu
Mihailov, Evelin
Fox, Caroline
Liu, Ching-Ti
Rybin, Denis
Isomaa, Bo
Lyssenko, Valeriya
Tuomi, Tiinamaija
Peltonen, Leena
Kovacs, Peter
Couper, David J
Pankow, James S
Grarup, Niels
Have, Christian T
Jørgensen, Marit E
Jørgensen, Torben
Linneberg, Allan
Cornelis, Marilyn C
van Dam, Rob M
Hunter, David J
Tonjes, Anke
Tikkanen, Emmi
Kraft, Peter
Sun, Qi
Edkins, Sarah
Owen, Katharine R
Perry, John R B
Wood, Andrew R
Zeggini, Eleftheria
Tajes-Fernandes, Juan
Abecasis, Goncalo R
Maruthur, Nisa M
Bonnycastle, Lori L
Charpentier, Guillaume
Chines, Peter S
Stringham, Heather M
Koistinen, Heikki A
Kinnunen, Leena
Sennblad, Bengt
Mühleisen, Thomas W
Nöthen, Markus M
Pechlivanis, Sonali
Scapoli, Chiara
Baldassarre, Damiano
Gertow, Karl
Eury, Elodie
Humphries, Steve E
Tremoli, Elena
Klopp, Norman
Meyer, Julia
Steinbach, Gerald
Lobbens, Stéphane
Gigante, Bruna
Erbel, Raimund
Leander, Karin
Ferreira, Teresa
McLeod, Olga
Bottinger, Erwin P
Gottesman, Omri
Lee, Yeji
Jöckel, Karl-Heinz
Moebus, Susanne
Rayner, Nigel W
de Faire, Ulf
Hamsten, Anders
Stumvoll, Michael
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Issue Date
2017-11

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Citation
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans. 2017, 66 (11):2888-2902 Diabetes
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 < 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.
Description
To access publisher's full text version of this article click on the hyperlink below
Additional Links
http://diabetes.diabetesjournals.org/content/66/11/2888
Rights
Archived with thanks to Diabetes
ae974a485f413a2113503eed53cd6c53
10.2337/db16-1253
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English Journal Articles (Peer Reviewed)

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