Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

Morris, A. P. et al. (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics, 44(9), pp. 981-990. (doi:10.1038/ng.2383) (PMID:22885922) (PMCID:PMC3442244)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Strawbridge, Dr Rona
Authors: 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.'a., 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., 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., and McCarthy, M. I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Nature Genetics
Publisher:Nature Publishing Group
ISSN:1061-4036
ISSN (Online):1546-1718
Published Online:12 August 2012

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