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

GIANT Consortium, MAGIC Investigators, 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 McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J. Willer, Soumya Raychaudhuri, Steve A. McCarroll, Claudia LangenbergOliver M. Hofmann, Josee 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, Andrew Morris, Igor Rudan, Harry Campbell, James F. Wilson

Research output: Contribution to journalArticlepeer-review

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

  • Polymorphism, Single Nucleotide
  • Genome, Human
  • Humans
  • Fasting
  • Genetic Heterogeneity
  • Blood Glucose
  • Genome-Wide Association Study
  • Gene Expression Profiling
  • Dual-Specificity Phosphatases
  • KCNQ1 Potassium Channel
  • Diabetes Mellitus, Type 2
  • Mitogen-Activated Protein Kinase Phosphatases
  • Hepatocyte Nuclear Factor 1-alpha
  • Genetic Predisposition to Disease
  • Gene Dosage
  • Meta-Analysis as Topic

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