Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)^{1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11}. Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 10^{- 14}), CDC123-CAMK1D (P = 1.2 10^{- 10}), TSPAN8-LGR5 (P = 1.1 10^{- 9}), THADA (P = 1.1 10^{- 9}), ADAMTS9 (P = 1.2 10^{- 8}) and NOTCH2 (P = 4.1 10^{- 8}) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
2. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
3. Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02142, USA.
4. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
5. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
6. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
7. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
8. Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
9. The full list of authors and affiliations appears at the end of this paper.
10. These authors contributed equally to this work.
11. Department of Statistics, University of Oxford, Oxford, OX1 3TG, UK.
12. Division of Genetics, Brigham and Women's Hospital, Harvard-Partners Center for Genetics and Genomics, Boston, Massachusetts 02115, USA.
13. Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, University Hospital Malmö, Lund University, S-205 02 Malmö, Sweden.
14. Steno Diabetes Center, Copenhagen, DK-2820, Denmark.
15. Skaraborg Institute, S-541 30 Skövde, Sweden.
16. Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
17. Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
18. Faculty of Health Science, University of Aarhus, Aarhus, DK-8000, Denmark.
19. Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, Massachusetts 02139, USA.
20. Diabetes Research Group, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
21. Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, EX1 2LU, UK.
22. Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, UK.
23. Gesellschaft für Strahlenforschung-National Research Center for Environment and Health, Institute of Epidemiology, D-85764 Neuherberg, Germany.
24. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LJ, UK.
25. Institute for Clinical Diabetes Research, German Diabetes Center, Leibniz Institute at Heinrich Heine University, D-40225 Düsseldorf, Germany.
26. Centre for Diabetes and Metabolic Medicine, Barts and The London, Royal London Hospital, Whitechapel, London, E1 1BB, UK.
27. Malmska Municipal Health Center and Hospital, FIN-68601 Jakobstad, Finland.
28. Folkhälsan Research Center, FIN-00014 Helsinki, Finland.
29. Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
30. deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
31. Department of Medicine, University of Kuopio and Kuopio University Hospital, 70210, Kuopio, Finland.
32. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
33. Department of General Practice, University of Aarhus, DK-8000 Aarhus, Denmark.
34. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
35. HUNT Research Centre, Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7650 Verdal, Norway.
36. Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
37. Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
38. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7600 Levanger, Norway.
39. Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
40. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
41. The MRC Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Road, Bristol, BS2 8PR, UK.
42. Department of Medicine, Helsinki University Hospital, University of Helsinki, FIN-00300 Helsinki, Finland.
43. Diabetes Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, 00300 Helsinki, Finland.
44. Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
45. South Ostrobothnia Central Hospital, 60220 Seinäjoki, Finland.
46. Diabetes Research Group, School of Clinical Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
47. Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
48. Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
49. Membership of the Wellcome Trust Case Control Consortium is provided in the Supplementary Note.
50. These authors contributed equally to this work.

Correspondence to: Mark I McCarthy^1,24,50 e-mail: mark.mccarthy@drl.ox.ac.uk

Correspondence to: Michael Boehnke^2,50 e-mail: boehnke@umich.edu

Correspondence to: David Altshuler^{3,4,6,7,8,48,50} e-mail: altshuler@molbio.mgh.harvard.edu

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