An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
Creators: name: Zeggini, Eleftheria
name: Gertow, Karl
name: Salomaa, Veikko
name: Eicher, John D.
name: Hamsten, Anders
name: Prokopenko, Inga
name: Donnelly, Peter J.
name: Perry, John R B
name: Jiang, Longda
name: Benediktsson, Rafn
name: Strawbridge, Rona J.
name: Johnson, Andrew D.
name: Cornelis, Marilyn C.
name: Strauch, Konstantin
name: Kaakinen, Marika
name: Florez, Jose C.
name: Sijbrands, Eric
name: Jørgensen, Marit E.
name: Barroso, Inês
name: Leander, Karin
name: Mühleisen, Thomas W.
name: Ruderfer, Douglas
name: Mӓnnistö, Satu
name: Grallert, Harald
name: Boerwinkle, Eric
name: Isomaa, Bo
name: Steinbach, Gerald
name: Gustafsson, Stefan
name: Frånberg, Mattias
name: van Leeuwen, Elisabeth M.
name: Rayner, Nigel W.
name: Tajes-Fernandes, Juan
name: Sigurðsson, Gunnar
name: Kraft, Peter
name: Edkins, Sarah
name: Pankow, James S.
name: Steinthorsdottir, Valgerdur
name: Boeing, Heiner
name: Wennauer, Roman
name: Wareham, Nicholas J.
name: Pedersen, Oluf
name: Kerrison, Nicola D.
name: de Faire, Ulf
name: Eisele, Lewin
name: Pedersen, Nancy L.
name: Liang, Liming
name: Franks, Paul W.
name: Robertson, Neil
name: Ripatti, Samuli
name: Jackson, Anne U.
name: Metspalu, Andres
name: Ferreira, Teresa
name: Koistinen, Heikki A.
name: Tuomi, Tiinamaija
name: Bottinger, Erwin P.
name: Meitinger, Thomas
name: Lu, Yingchang
name: Scapoli, Chiara
name: Dupuis, Josée
name: van der Schouw, Yvonne T.
name: Stringham, Heather M.
name: Humphries, Steve E.
name: Lyssenko, Valeriya
name: Cauchi, Stephane
name: Froguel, Philippe
name: Dina, Christian
name: Chen, Han
name: Grarup, Niels
name: Kwan, Phoenix
name: McCarthy, Mark I.
name: Liu, Ching-Ti
name: Scott, Laura J.
name: Esko, Tõnu
name: Kong, Augustine
name: Tuomilehto, Jaakko
name: Palli, Domenico
name: Ma, Clement
name: Marullo, Letizia
name: Blüher, Matthias
name: Lobbens, Stéphane
name: Sparso, Thomas
name: Mihailov, Evelin
name: Langenberg, Claudia
name: Ried, Janina S.
name: Fuchsberger, Christian
name: Hunter, David J.
name: Palmer, Colin N A
name: Thorsteinsdottir, Unnur
name: Deloukas, Panagiotis
name: Hreidarsson, Astradur B.
name: Yengo, Loic
name: Qi, Lu
name: Lannfelt, Lars
name: Hattersley, Andrew T.
name: Peltonen, Leena
name: Fox, Caroline
name: Roden, Michael
name: Collins, Francis S.
name: Mägi, Reedik
name: Jørgensen, Torben
name: Lindgren, Cecilia M.
name: Gottesman, Omri
name: Boehm, Bernhard O.
name: Thorand, Barbara
name: Sun, Qi
name: Frayling, Timothy M.
name: Baldassarre, Damiano
name: Loos, Ruth J F
name: Morris, Andrew D.
name: Kinnunen, Leena
name: Nöthen, Markus M.
name: Bergman, Richard N.
name: Van Zuydam, Natalie R.
name: Barricarte Gurrea, Aurelio
name: Stumvoll, Michael
name: Gigante, Bruna
name: Thorleifsson, Gudmar
name: van Dam, Rob M.
name: Ingelsson, Erik
name: Teslovich, Tanya M.
name: Luan, Jian'an
name: Li, Man
name: Altshuler, David
name: Groop, Leif C.
name: Boehnke, Michael
name: Pers, Tune H.
name: Mahajan, Anubha
name: Lind, Lars
name: Karssen, Lennart C.
name: Sennblad, Bengt
name: Hansen, Torben
name: Klopp, Norman
name: van Duijn, Cornelia M.
name: Pechlivanis, Sonali
name: Balkau, Beverley
name: Stefansson, Kari
name: Tikkanen, Emmi
name: Maruthur, Nisa M.
name: Abecasis, Goncalo R.
name: Meyer, Julia
name: Lee, Yeji
name: Kovacs, Peter
name: Have, Christian T.
name: Chanda, Pritam
name: Kestler, Hans A.
name: Chheda, Himanshu
name: Wood, Andrew R.
name: Thuillier, Dorothee
name: Owen, Katharine R.
name: Hu, Frank B.
name: Gaulton, Kyle J.
name: Linneberg, Allan
name: Voight, Ben F.
name: Gieger, Christian
name: Bonnycastle, Lori L.
name: Eury, Elodie
name: Tremoli, Elena
name: Scott, Robert A.
name: Moebus, Susanne
name: Chines, Peter S.
name: Tonjes, Anke
name: Mohlke, Karen L.
name: Morris, Andrew P.
name: Eriksson, Johan G.
name: Almgren, Peter
name: Pervjakova, Natalia
name: Müller-Nurasyid, Martina
name: Erbel, Raimund
name: Charpentier, Guillaume
name: Couper, David J.
name: Willems, Sara M.
name: Meigs, James B.
name: Jöckel, Karl-Heinz
name: McLeod, Olga
name: Rybin, Denis
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: To characterise 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 cases and 132,532 controls of European ancestry after imputation using the 1000 Genomes multi-ethnic reference panel. Promising association signals were followed-up in additional data sets (of 14,545 or 7,397 T2D cases and 38,994 or 71,604 controls). 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 SNVs. 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.