An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
| Autor: | Rob M. van Dam, Francis S. Collins, Konstantin Strauch, Raimund Erbel, Rafn Benediktsson, Philippe Froguel, Kyle J. Gaulton, Peter Donnelly, Torben Hansen, Longda Jiang, Lennart C. Karssen, Rona J. Strawbridge, David J. Hunter, Leena Kinnunen, Thomas Meitinger, Michael Stumvoll, Stéphane Cauchi, Ching-Ti Liu, Olga McLeod, Oluf Pedersen, Michael Boehnke, Denis Rybin, Karl Gertow, Tõnu Esko, Bernhard O. Boehm, Sonali Pechlivanis, Bo Isomaa, Anne U. Jackson, Clement Ma, Yingchang Lu, Nicola D. Kerrison, Ruth J. F. Loos, Caroline S. Fox, Chiara Scapoli, Jian'an Luan, Martina Müller-Nurasyid, Domenico Palli, Anke Tönjes, Natalie R. van Zuydam, Neil Robertson, Barbara Thorand, Natalia Pervjakova, Andrew R. Wood, Karin Leander, Unnur Thorsteinsdottir, Sara M. Willems, Karen L. Mohlke, Robert A. Scott, Markus M. Nöthen, Ulf de Faire, Qi Sun, Eric Boerwinkle, Roman Wennauer, Douglas M. Ruderfer, Marika Kaakinen, Nigel W. Rayner, Jaakko Tuomilehto, Nisa M. Maruthur, Richard N. Bergman, Janina S. Ried, Himanshu Chheda, Josée Dupuis, Juan Tajes-Fernandes, Steve E. Humphries, Reedik Mägi, Gonçalo R. Abecasis, B F Voight, David Couper, Cornelia M. van Duijn, Samuli Ripatti, Yeji Lee, Heikki A. Koistinen, Christian Dina, Andres Metspalu, Lu Qi, James S. Pankow, Han Chen, Damiano Baldassarre, Mattias Frånberg, Gerald Steinbach, Inga Prokopenko, Matthias Blüher, Jose C. Florez, Julia Meyer, Niels Grarup, Anders Hamsten, Valeriya Lyssenko, James B. Meigs, Pritam Chanda, Leif Groop, Sarah Edkins, Anubha Mahajan, Gunnar Sigurðsson, Marilyn C. Cornelis, Christian Gieger, Nancy L. Pedersen, Andrew T. Hattersley, Paul W. Franks, Nicholas J. Wareham, Stefan Gustafsson, Katharine R. Owen, Peter Kovacs, Andrew D. Johnson, Lori L. Bonnycastle, Tiinamaija Tuomi, Aurelio Barricarte Gurrea, Tune H. Pers, Eric J.G. Sijbrands, Phoenix Kwan, Emmi Tikkanen, Elisabeth M. van Leeuwen, Stéphane Lobbens, Claudia Langenberg, E. Eury, Thomas W. Mühleisen, Lewin Eisele, Veikko Salomaa, Satu Mӓnnistö, Christian Fuchsberger, Evelin Mihailov, David Altshuler, Timothy M. Frayling, Peter Almgren, Harald Grallert, Hans A. Kestler, Beverley Balkau, Erik Ingelsson, Colin N. A. Palmer, Yvonne T. van der Schouw, Michael Roden, Thomas Sparsø, Karl-Heinz Jöckel, Johan G. Eriksson, Inês Barroso, John D. Eicher, Bengt Sennblad, Bruna Gigante, Andrew D. Morris, Panagiotis Deloukas, Man Li, Allan Linneberg, Astradur B. Hreidarsson, Lars Lannfelt, Elena Tremoli, Liming Liang, Omri Gottesman, Letizia Marullo, Peter S. Chines, Kari Stefansson, Mark I. McCarthy, Andrew P. Morris, Erwin P. Bottinger, Augustine Kong, Torben Jørgensen, Tanya M. Teslovich, Frank B. Hu, Dorothée Thuillier, Peter Kraft, Heiner Boeing, Laura J. Scott, Gudmar Thorleifsson, Lars Lind, John R. B. Perry, Heather M. Stringham, Susanne Moebus, Valgerdur Steinthorsdottir, Cecilia M. Lindgren, Guillaume Charpentier, Eleftheria Zeggini, Leena Peltonen, Loic Yengo, Norman Klopp, Teresa Ferreira, Christian Theil Have, Marit E. Jørgensen |
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| Přispěvatelé: | Epidemiology, Erasmus MC other, Internal Medicine, Luan, Jian'an [0000-0003-3137-6337], Perry, John [0000-0001-6483-3771], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Commission of the European Communities, Wellcome Trust |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
PROVIDES
0301 basic medicine SUSCEPTIBILITY LOCI endocrine system diseases Endocrinology Diabetes and Metabolism PATHOPHYSIOLOGY European Continental Ancestry Group Medizin Genome-wide association study Biology Quantitative trait locus Bioinformatics White People GENETIC ARCHITECTURE NO Endocrinology & Metabolism 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being Diabetes Mellitus Type 2 European Continental Ancestry Group Gene Expression Regulation Genetic Variation Genome-Wide Association Study Humans Diabetes Mellitus Internal Medicine Journal Article Glucose homeostasis Humans 1000 Genomes Project Allele frequency METAANALYSIS 11 Medical and Health Sciences RISK Genetics Science & Technology RECEPTOR DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium Haplotype Genetic Variation nutritional and metabolic diseases Genetic architecture 030104 developmental biology Diabetes Mellitus Type 2 Gene Expression Regulation RARE VARIANTS LOW-FREQUENCY Life Sciences & Biomedicine Type 2 030217 neurology & neurosurgery Imputation (genetics) FASTING GLUCOSE Genome-Wide Association Study |
| Zdroj: | 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, N W, Robertson, N R, 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, Jørgensen, T & DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium 2017, ' An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans ', Diabetes, vol. 66, no. 11, pp. 2888-2902 . https://doi.org/10.2337/db16-1253 Diabetes 66, 2888-2902 (2017) Diabetes, 66(11), 2888-2902. American Diabetes Association Inc. 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, 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, Tonjes, A, Maruthur, N M, Scapoli, C, Erbel, R, Jöckel, K, 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 2017, ' An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans ', Diabetes, pp. db161253 . https://doi.org/10.2337/db16-1253 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, N W, 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, Jørgensen, M E, Hansen, T & DIAGRAM Consortium 2017, ' An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans ', Diabetes, vol. 66, no. 11, pp. 2888-2902 . https://doi.org/10.2337/db16-1253 Diabetes Diabetes, 66(11), 2888. American Diabetes Association Inc. DIABETES |
| ISSN: | 0012-1797 |
| DOI: | 10.2337/db16-1253 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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