Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Benjamin F. Voight, Laura J. Scott, Valgerdur Steinthorsdottir, Andrew P. Morris, Christian Dina, Ryan P. Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S. Aulchenko, Gudmar Thorleifsson, Laura J. McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J. Willer, Soumya Raychaudhuri, Steve A. McCarroll, Claudia Langenberg, Oliver M. HofmannJosee Dupuis, Lu Qi, Ayellet V. Segre, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J. Bennett, Roza Blagieva, Eric Boerwinkle, Lori L. Bonnycastle, Kristina Bengtsson Bostrom, Bert Bravenboer, Suzannah Bumpstead, Noisel P. Burtt, Guillaume Charpentier, Peter S. Chines, Marilyn Cornelis, David J. Couper, Gabe Crawford, Alex S. F. Doney, Katherine S. Elliott, Amanda L. Elliott, Michael R. Erdos, Caroline S. Fox, Christopher S. Franklin, Martha Ganser, Andrew D. Morris, Colin N. A. Palmer, GIANT Consortium, MAGIC Investigators

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    1266 Citations (Scopus)

    Abstract

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

    Original languageEnglish
    Pages (from-to)579-U155
    Number of pages13
    JournalNature Genetics
    Volume42
    Issue number7
    DOIs
    Publication statusPublished - Jul 2010

    Keywords

    • GENOME-WIDE ASSOCIATION
    • C-REACTIVE PROTEIN
    • FASTING PLASMA-GLUCOSE
    • QT INTERVAL DURATION
    • INSULIN-RESISTANCE
    • COMMON VARIANTS
    • COMPLEX DISEASES
    • GENE-EXPRESSION
    • HNF1-ALPHA GENE
    • CROHNS-DISEASE

    Cite this

    Voight, B. F., Scott, L. J., Steinthorsdottir, V., Morris, A. P., Dina, C., Welch, R. P., Zeggini, E., Huth, C., Aulchenko, Y. S., Thorleifsson, G., McCulloch, L. J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C. J., Raychaudhuri, S., McCarroll, S. A., Langenberg, C., ... GIANT Consortium, MAGIC Investigators (2010). Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature Genetics, 42(7), 579-U155. https://doi.org/10.1038/ng.609