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

DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Wellcome Trust Case Control Consortium, MAGIC Investigators, GIANT Consortium, , Andrew P. Morris, Benjamin F. Voight, Tanya M. Teslovich, Teresa Ferreira, Ayellet V. Segre, Valgerdur Steinthorsdottir, Rona J. Strawbridge, Hassan Khan, Harald Grallert, Anubha Mahajan, Inga Prokopenko, Hyun Min Kang, Christian Dina, Tonu Esko, Ross M. FraserStavroula Kanoni, Ashish Kumar, Vasiliki Lagou, Claudia Langenberg, Jian'an Luan, Cecilia M. Lindgren, Martina Mueller-Nurasyid, Sonali Pechlivanis, N. William Rayner, Laura J. Scott, Steven Wiltshire, Loic Yengo, Leena Kinnunen, Elizabeth J. Rossin, Soumya Raychaudhuri, Andrew D. Johnson, Antigone S. Dimas, Ruth J. F. Loos, Sailaja Vedantam, Han Chen, Jose C. Florez, Caroline Fox, Ching-Ti Liu, Denis Rybin, David J. Couper, Wen Hong L. Kao, Man Li, Marilyn C. Cornelis, Peter Kraft, Qi Sun, Rob M. van Dam, Heather M. Stringham, Alex S. F. Doney, Colin N. A. Palmer, Andrew D. Morris, South Asian Type 2 Diabetes SAT2D Consortium

    Research output: Contribution to journalArticle

    1156 Citations (Scopus)

    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. Genomewide 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.

    Original languageEnglish
    Pages (from-to)981-990
    Number of pages12
    JournalNature Genetics
    Volume44
    Issue number9
    DOIs
    Publication statusPublished - Sep 2012

    Cite this

    DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Wellcome Trust Case Control Consortium, MAGIC Investigators, GIANT Consortium, Morris, A. P., Voight, B. F., Teslovich, T. M., Ferreira, T., Segre, A. V., Steinthorsdottir, V., Strawbridge, R. J., Khan, H., Grallert, H., Mahajan, A., Prokopenko, I., Kang, H. M., Dina, C., Esko, T., ... South Asian Type 2 Diabetes SAT2D Consortium (2012). Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature Genetics, 44(9), 981-990. https://doi.org/10.1038/ng.2383