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Scott, R.A.* ; Scott, L.J.* ; Mägi, R.* ; Marullo, L.* ; Gaulton, K.J.* ; Kaakinen, M.* ; Pervjakova, N.* ; Pers, T.H.* ; Johnson, A.D.* ; Eicher, J.D.* ; Jackson, A.U.* ; Ferreira, T.* ; Lee, Y.* ; Ma, C.* ; Steinthorsdottir, V.* ; Thorleifsson, G.* ; Qi, L.* ; van Zuydam, N.R.* ; Mahajan, A.* ; Chen, H.* ; Almgren, P.* ; Voight, B.F.* ; Grallert, H. ; Müller-Nurasyid, M. ; Ried, J.S. ; Rayner, W.N.* ; Robertson, N.* ; Karssen, L.C.* ; van Leeuwen, E.M.* ; Willems, S.M.* ; Fuchsberger, C.* ; Kwan, P.* ; Teslovich, T.M.* ; Chanda, P.* ; Li, M.* ; Lu, Y.* ; Dina, C.* ; Thuillier, D.* ; Yengo, L.* ; Jiang, L.* ; Sparso, T.* ; Kestler, H.A.* ; Chheda, H.* ; Eisele, L.* ; Gustafsson, S.* ; Frånberg, M.* ; Strawbridge, R.J.* ; Benediktsson, R.* ; Hreidarsson, A.B.* ; Kong, A.* ; Sigurðsson, G.* ; Kerrison, N.D.* ; Luan, J.* ; Liang, L.* ; Meitinger, T. ; Roden, M.* ; Thorand, B. ; Esko, T.* ; Mihailov, E.* ; Fox, C.* ; Liu, C.-T.* ; Rybin, D.* ; Isomaa, B.* ; Lyssenko, V.* ; Tuomi, T.* ; Couper, D.J.* ; Pankow, J.S.* ; Grarup, N.* ; Have, C.T.* ; Jørgensen, M.E.* ; Jørgensen, T.* ; Linneberg, A.* ; Cornelis, M.C.* ; van Dam, R.M.* ; Hunter, D.J.* ; Kraft, P.* ; Sun, Q.* ; Edkins, S.* ; Owen, K.R.* ; Perry, J.R.* ; Wood, A.R.* ; Zeggini, E.* ; Tajes-Fernandes, J.* ; Abecasis, G.R.* ; Bonnycastle, L.L.* ; Chines, P.S.* ; Stringham, H.M.* ; Koistinen, H.A.* ; Kinnunen, L.* ; Sennblad, B.* ; Mühleisen, T.W.* ; Nöthen, M.M.* ; Pechlivanis, S.* ; Baldassarre, D.* ; Gertow, K.* ; Humphries, S.E.* ; Tremoli, E.* ; Klopp, N. ; Meyer, J. ; Steinbach, G.* ; Wennauer, R.* ; Eriksson, J.G.* ; Mӓnnistö, S.* ; Peltonen, L.* ; Tikkanen, E.* ; Charpentier, G.* ; Eury, E.* ; Lobbens, S.* ; Gigante, B.* ; Leander, K.* ; McLeod, O.* ; Bottinger, E.P.* ; Gottesman, O.* ; Ruderfer, D.* ; Blüher, M.* ; Kovacs, P.* ; Tönjes, A.* ; Maruthur, N.M.* ; Scapoli, C.* ; Erbel, R.* ; Jöckel, K.H.* ; Moebus, S.* ; de Faire, U.* ; Hamsten, A.* ; Stumvoll, M.* ; Deloukas, P.* ; Donnelly, P.J.* ; Frayling, T.M.* ; Hattersley, A.T.* ; Ripatti, S.* ; Salomaa, V.* ; Pedersen, N.L.* ; Boehm, B.O.* ; Bergman, R.N.* ; Collins, F.S.* ; Mohlke, K.L.* ; Tuomilehto, J.* ; Hansen, T.* ; Pedersen, O.* ; Barroso, I.* ; Lannfelt, L.* ; Ingelsson, E.* ; Lind, L.* ; Lindgren, C.M.* ; Cauchi, S.* ; Froguel, P.* ; Loos, R.J.* ; Balkau, B.* ; Boeing, H.* ; Franks, P.W.* ; Gurrea, A.B.* ; Palli, D.* ; van der Schouw, Y.T.* ; Altshuler, D.* ; Groop, L.C.* ; Langenberg, C.* ; Wareham, N.J.* ; Sijbrands, E.* ; van Duijn, C.M.* ; Florez, J.C* ; Meigs, J.B.* ; Boerwinkle, E.* ; Gieger, C. ; Strauch, K. ; Metspalu, A.* ; Morris, A.D.* ; Palmer, C.N.* ; Hu, F.B.* ; Thorsteinsdottir, U.* ; Stefansson, K.* ; Dupuis, J.* ; Morris, A.P.* ; Boehnke, M.* ; McCarthy, M.I.* ; Prokopenko, I.*

An expanded genome-wide association study of type 2 diabetes in Europeans.

Diabetes 66, 2888-2902 (2017)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Body-mass Index; Genetic Architecture; Susceptibility Loci; Low-frequency; Glucose-homeostasis; Fasting Glucose; Rare Variants; Risk; Disease; Receptor
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 66, Issue: 11, Pages: 2888-2902 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)