Cited by 1,912Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsDiabetes and associated disorders
Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes
Open accessthe DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Morris, Andrew P, Voight, Benjamin F, Teslovich, Tanya M, Ferreira, Teresa, Segrè, Ayellet V, Steinthorsdottir, Valgerdur, Strawbridge, Rona J +202 more·2012·Nature Genetics
DOI 10.1038/ng.2383PMC PMC3442244
Abstract
To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
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Over 50 gene loci have been linked to type 2 diabetes using GWAS.
“over 50 gene loci have been linked to type 2 diabetes19.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [19]
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References 59 · Cited by 1,912
- Authors
- the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Morris, A. P., Voight, B. F., Teslovich, T. M., Ferreira, T., Segrè, A. V., Steinthorsdottir, V., Strawbridge, R. J., Khan, H., Grallert, H., Mahajan, A., Prokopenko, I., Kang, H. M., Dina, C., Esko, T., Fraser, R. M., Kanoni, S., Kumar, A., Lagou, V., Langenberg, C., Luan, J., Lindgren, C. M., Müller-Nurasyid, M., Pechlivanis, S., Rayner, N. W., Scott, L. J., Wiltshire, S., Yengo, L., Kinnunen, L., Rossin, E. J., Raychaudhuri, S., Johnson, A. D., Dimas, A. S., Loos, R. J. F., Vedantam, S., Chen, H., Florez, J. C., Fox, C., Liu, C.-T., Rybin, D., Couper, D. J., Kao, W. H. L., Li, M., Cornelis, M. C., Kraft, P., Sun, Q., van Dam, R. M., Stringham, H. M., Chines, P. S., Fischer, K., Fontanillas, P., Holmen, O. L., Hunt, S. E., Jackson, A. U., Kong, A., Lawrence, R., Meyer, J., Perry, J. R. B., Platou, C. G. P., Potter, S., Rehnberg, E., Robertson, N., Sivapalaratnam, S., Stančáková, A., Stirrups, K., Thorleifsson, G., Tikkanen, E., Wood, A. R., Almgren, P., Atalay, M., Benediktsson, R., Bonnycastle, L. L., Burtt, N., Carey, J., Charpentier, G., Crenshaw, A. T., Doney, A. S. F., Dorkhan, M., Edkins, S., Emilsson, V., Eury, E., Forsen, T., Gertow, K., Gigante, B., Grant, G. B., Groves, C. J., Guiducci, C., Herder, C., Hreidarsson, A. B., Hui, J., James, A., Jonsson, A., Rathmann, W., Klopp, N., Kravic, J., Krjutškov, K., Langford, C., Leander, K., Lindholm, E., Lobbens, S., Männistö, S., Mirza, G., Mühleisen, T. W., Musk, B., Parkin, M., Rallidis, L., Saramies, J., Sennblad, B., Shah, S., Sigurðsson, G., Silveira, A., Steinbach, G., Thorand, B., Trakalo, J., Veglia, F., Wennauer, R., Winckler, W., Zabaneh, D., Campbell, H., van Duijn, C., Uitterlinden, A. G., Hofman, A., Sijbrands, E., Abecasis, G. R., Owen, K. R., Zeggini, E., Trip, M. D., Forouhi, N. G., Syvänen, A.-C., Eriksson, J. G., Peltonen, L., Nöthen, M. M., Balkau, B., Palmer, C. N. A., Lyssenko, V., Tuomi, T., Isomaa, B., Hunter, D. J., Qi, L., Wellcome Trust Case Control Consortium, Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Asian Genetic Epidemiology Network–Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Shuldiner, A. R., Roden, M., Barroso, I., Wilsgaard, T., Beilby, J., Hovingh, K., Price, J. F., Wilson, J. F., Rauramaa, R., Lakka, T. A., Lind, L., Dedoussis, G., Njølstad, I., Pedersen, N. L., Khaw, K.-T., Wareham, N. J., Keinanen-Kiukaanniemi, S. M., Saaristo, T. E., Korpi-Hyövälti, E., Saltevo, J., Laakso, M., Kuusisto, J., Metspalu, A., Collins, F. S., Mohlke, K. L., Bergman, R. N., Tuomilehto, J., Boehm, B. O., Gieger, C., Hveem, K., Cauchi, S., Froguel, P., Baldassarre, D., Tremoli, E., Humphries, S. E., Saleheen, D., Danesh, J., Ingelsson, E., Ripatti, S., Salomaa, V., Erbel, R., Jöckel, K.-H., Moebus, S., Peters, A., Illig, T., de Faire, U., Hamsten, A., Morris, A. D., Donnelly, P. J., Frayling, T. M., Hattersley, A. T., Boerwinkle, E., Melander, O., Kathiresan, S., Nilsson, P. M., Deloukas, P., Thorsteinsdottir, U., Groop, L. C., Stefansson, K., Hu, F., Pankow, J. S., Dupuis, J., Meigs, J. B., Altshuler, D., Boehnke, M., & McCarthy, M. I.
- Affiliations
- Centre for Human Genetics (GB)
- Broad Institute (US)
- University of Michigan (US)
- Karolinska University Hospital (SE)
- University of Cambridge (GB)
- Helmholtz Munich (DE)
- University of Edinburgh (GB)
- Wellcome Sanger Institute (GB)
- Addenbrooke's Hospital (GB)
- Essen University Hospital (DE)
- Finnish Institute for Health and Welfare (FI)
- Framingham Heart Study (US)
- University of Geneva (CH)
- Boston University (US)
- Brigham and Women's Hospital (US)
- University of North Carolina at Chapel Hill (US)
- Johns Hopkins University (US)
- Harvard University (US)
- National Institutes of Health (US)
- University of Tartu (EE)
- Norwegian University of Science and Technology (NO)
- deCODE Genetics (Iceland) (IS)
- The University of Western Australia (AU)
- Karolinska Institutet (SE)
- Amsterdam UMC Location University of Amsterdam (NL)
- University of Eastern Finland (FI)
- University of Exeter (GB)
- Lund University (SE)
- University of Iceland (IS)
- Centre Hospitalier Sud Francilien (FR)
- University of Dundee (GB)
- Icelandic Heart Association (IS)
- Centre National de la Recherche Scientifique (FR)
- University of Oxford (GB)
- Deutsches Diabetes-Zentrum e.V. (DE)
- University of Bonn (DE)
- South Karelia Central Hospital (FI)
- University College London (GB)
- Universität Ulm (DE)
- Centro Cardiologico Monzino (IT)
- Western General Hospital (GB)
- Erasmus MC (NL)
- Churchill Hospital (GB)
- Uppsala University (SE)
- University of Helsinki (FI)
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- Folkhälsans Forskningscentrum (FI)
- University of Maryland, Baltimore (US)
- UiT The Arctic University of Norway (NO)
- Kuopio University Hospital (FI)
- Harokopio University of Athens (GR)
- Oulu University Hospital (FI)
- Finnish Diabetes Association (FI)
- Seinäjoen Keskussairaala (FI)
- Central Finland Health Care District (FI)
- Cedars-Sinai Medical Center (US)
- Universität für Weiterbildung Krems (AT)
- University of Milan (IT)
- Baylor College of Medicine (US)
- University of Minnesota (US)
- Corresponding author
- Morris, Andrew P
- Morris, Andrew D
- Boehnke, Michael
- McCarthy, Mark I
- ORCID
- Morris, Andrew P
- Voight, Benjamin F
- Ferreira, Teresa
- Segrè, Ayellet V
- Strawbridge, Rona J
- Khan, Hassan
- Grallert, Harald
- Mahajan, Anubha
- Prokopenko, Inga
- Kang, Hyun Min
- Fraser, Ross M
- Kanoni, Stavroula
- Kumar, Ashish
- Lagou, Vasiliki
- Langenberg, Claudia
- Luan, Jian'an
- Lindgren, Cecilia M
- Pechlivanis, Sonali
- Rayner, N William
- Scott, Laura J
- Kinnunen, Leena
- Rossin, Elizabeth J
- Raychaudhuri, Soumya
- Johnson, Andrew D
- Dimas, Antigone S
- Loos, Ruth J F
- Vedantam, Sailaja
- Chen, Han
- Fox, Caroline
- Liu, Ching-Ti
- Rybin, Denis
- Couper, David J
- Li, Man
- Kraft, Peter
- Sun, Qi
- Stringham, Heather M
- Fischer, Krista
- Fontanillas, Pierre
- Hunt, Sarah E
- Kong, Augustine
- Meyer, Julia
- Perry, John R B
- Potter, Simon
- Rehnberg, Emil
- Robertson, Neil
- Sivapalaratnam, Suthesh
- Stirrups, Kathleen
- Tikkanen, Emmi
- Wood, Andrew R
- Almgren, Peter
- Atalay, Mustafa
- Benediktsson, Rafn
- Bonnycastle, Lori L
- Burtt, Noël
- Charpentier, Guillaume
- Doney, Alex S F
- Dorkhan, Mozhgan
- Edkins, Sarah
- Emilsson, Valur
- Gigante, Bruna
- Herder, Christian
- Hui, Jennie
- Jonsson, Anna
- Rathmann, Wolfgang
- Krjutškov, Kaarel
- Langford, Cordelia
- Leander, Karin
- Lindholm, Eero
- Männistö, Satu
- Sennblad, Bengt
- Shah, Sonia
- Silveira, Angela
- Thorand, Barbara
- Veglia, Fabrizio
- Winckler, Wendy
- Zabaneh, Delilah
- Sijbrands, Eric
- Owen, Katharine R
- Zeggini, Eleftheria
- Forouhi, Nita G
- Eriksson, Johan G
- Peltonen, Leena
- Nöthen, Markus M
- Balkau, Beverley
- Lyssenko, Valeriya
- Qi, Lu
- Shuldiner, Alan R
- Roden, Michael
- Wilsgaard, Tom
- Beilby, John
- Price, Jackie F
- Wilson, James F
- Lakka, Timo A
- Lind, Lars
- Dedoussis, George
- Njølstad, Inger
- Pedersen, Nancy L
- Khaw, Kay-Tee
- Wareham, Nicholas J
- Keinanen-Kiukaanniemi, Sirkka M
- Laakso, Markku
- Metspalu, Andres
- Collins, Francis S
- Mohlke, Karen L
- Bergman, Richard N
- Tuomilehto, Jaakko
- Boehm, Bernhard O
- Gieger, Christian
- Hveem, Kristian
- Froguel, Philippe
- Baldassarre, Damiano
- Tremoli, Elena
- Humphries, Steve E
- Saleheen, Danish
- Danesh, John
- Ingelsson, Erik
- Ripatti, Samuli
- Salomaa, Veikko
- Jöckel, Karl-Heinz
- Moebus, Susanne
- Peters, Annette
- Hamsten, Anders
- Morris, Andrew D
- Donnelly, Peter J
- Frayling, Timothy M
- Hattersley, Andrew T
- Boerwinkle, Eric
- Melander, Olle
- Kathiresan, Sekar
- Nilsson, Peter M
- Deloukas, Panos
- Groop, Leif C
- Hu, Frank
- Pankow, James S
- Dupuis, Josée
- Meigs, James B
- Altshuler, David
- Boehnke, Michael
- McCarthy, Mark I
- Venue
- Nature Genetics
- Published
- 2012-08-12
- Volume
- 44
- Issue
- 9
- Pages
- 981-990
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3442244
- OpenAlex
- W2045017910
- Cited by
- 1,912
- References
- 59
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- FWCI
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- FP7 People: Marie-Curie Actions
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 2 diabetes, genetic susceptibility loci, genetic architecture, common genetic variants, CREB-binding protein, adipocytokine signaling, cell cycle regulation, diabetes pathogenesis, European ancestry
- MeSH terms
- Diabetes Mellitus, Type 2, Female, Genes, Humans, Male, Pakistan, Sex Factors, Linkage Disequilibrium, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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