Abstract

We performed a genome-wide association analysis of 1,897,764 SNPs in 1,043 German ulcerative colitis (UC) cases and 1,703 controls. We discovered new associations at chromosome 7q22 (rs7809799) and at chromosome 22q13 in IL17REL (rs5771069) and confirmed these associations in six replication panels (2,539 UC cases and 5,428 controls) from different regions of Europe (overall study sample Prs7809799 = 8.81 × 10−11 and Prs5771069 = 4.21 × 10−8, respectively).

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Acknowledgements

We thank all individuals with UC and CD studied here, their families and physicians for their cooperation. We acknowledge the cooperation of the German Crohn and Colitis Foundation (Deutsche Morbus Crohn und Colitis Vereingung e.V.), the German Ministry of Education and Research (BMBF) competence network “IBD” and the contributing gastroenterologists. We thank E. Melum and K. Holm for discussion and support; T. Wesse, T. Henke, C. Fürstenau, S. Ehlers and R. Vogler for expert technical help; T. Wienker and M. Steffens (Institut für Medizinische Biometrie, Informatik und Epidemiologie, University of Bonn) for performing the quality control of the GWAS datasets; B.A. Lie and the Norwegian Bone Marrow Donor Registry at Rikshospitalet University Hospital, Oslo, for contributing the healthy Norwegian control population; and the following individuals for their invaluable participation in the collection of the Baltic (Lithuanian and Latvian) patient panel: G. Kiudelis, L. Jonaitis, A. Zvirbliene, G. Denapiene, A. Irnius, J. Valantinas, V. Svalbonas, D. Krukas, G. Simulionis, Z. Sukys, M. Leja and A. Derovs. This study was supported by the BMBF through the National Genome Research Network (NGFN), the PopGen Biobank and the Cooperative Research in the Region of Augsburg (KORA) research platform. KORA was initiated and financed by the Helmholtz Zentrum München–National Research Center for Environmental Health, which is funded by the German Federal Ministry of Education, Science, Research and Technology and by the State of Bavaria and the Munich Center of Health Sciences (MC Health) as part of the LMUinnovativ initiative. The project received infrastructure support through the Deutsche Forschungsgemeinschaft clusters of excellence Multimodal Computing and Interaction, Future Ocean, and Inflammation and Interfaces. We acknowledge use of DNA from the 1958 British Birth Cohort collection (courtesy of R. Jones, S. Ring, W. McArdle and M. Pembrey), funded by the UK Medical Research Council (grant G0000934) and the Wellcome Trust (grant 068545/Z/02). C.G.M. and C.M.O. were supported by The Wellcome Trust and Core (UK).

Author information

Author notes

    • Andre Franke
    • , Tobias Balschun
    • , Tom H Karlsen
    •  & Stefan Schreiber

    These authors contributed equally to this work.

Affiliations

  1. Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Christian-Albrechts University, Kiel, Germany.

    • Andre Franke
    • , Tobias Balschun
    • , David Ellinghaus
    • , Robert Häsler
    • , Michael Wittig
    • , Eva Buchert
    • , Philip Rosenstiel
    •  & Stefan Schreiber
  2. PopGen Biobank, University Hospital Schleswig-Holstein, Christian-Albrechts University, Kiel, Germany.

    • Christian Sina
    •  & Susanna Nikolaus
  3. Department of General Internal Medicine, University Hospital Schleswig-Holstein, Christian-Albrechts University, Kiel, Germany.

    • Christian Sina
    • , Susanna Nikolaus
    •  & Stefan Schreiber
  4. Max-Planck Institute for Informatics, Saarbrücken, Germany.

    • Gabriele Mayr
    •  & Mario Albrecht
  5. Institute of Epidemiology, Helmholtz Centre Munich, German Research Center for Environmental Health, Neuherberg, Germany.

    • Christian Gieger
    •  & H Erich Wichmann
  6. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians University, Munich, Germany.

    • H Erich Wichmann
  7. Klinikum Grosshadern, Munich, Germany.

    • H Erich Wichmann
  8. Department of Gastroenterology, Kaunas University of Medicine, Kaunas, Lithuania.

    • Jurgita Sventoraityte
    •  & Limas Kupcinskas
  9. Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.

    • Clive M Onnie
    •  & Christopher G Mathew
  10. Department of Biology, School of Medicine, University of Athens, Athens, Greece.

    • Maria Gazouli
    •  & Nicholas P Anagnou
  11. St. George's University, Division of Community Health Sciences, London, UK.

    • David Strachan
  12. Avon Longitudinal Study of Parents and Children, Department of Social Medicine, University of Bristol, Bristol, UK.

    • Wendy L McArdle
  13. Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.

    • Paul Rutgeerts
    •  & Séverine Vermeire
  14. Faculty of Medicine, Epigen, Akershus University Hospital, Oslo, Norway.

    • Morten H Vatn
  15. Medical Department, Rikshospitalet University Hospital, Oslo, Norway.

    • Morten H Vatn
    •  & Tom H Karlsen
  16. Institute of Medical Informatics and Statistics, Christian-Albrechts University, Kiel, Germany.

    • Michael Krawczak

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  1. and the IBSEN study group

    A full list of members is available in the Supplementary Note.

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Contributions

A.F. and T.B. performed SNP selection, genotyping and data analysis and prepared figures and tables. A.F. helped with data analysis. D.E. performed the imputation and generated the regional association plots. R.H. and P. Rosenstiel performed the expression analyses. E.B. helped with figures. M.W. was responsible for in-house conversion and quality assessment of GWAS data. M.K. helped with statistical analyses and interpretation of the results. S.N. and C.S. coordinated the recruitment and collected phenotype data of panels A and B. G.M. and M.A. performed the in silico protein analyses. C.G. and H.E.W. provided the KORA control samples. J.S., L.K., C.M.O., C.G.M., M.G., N.P.A., D.S., W.L.M., S.V., P. Rutgeerts, M.H.V. and the IBSEN study group provided the European replication samples and respective phenotypes. M.K., E.B., P. Rosenstiel and S.S. edited the manuscript. A.F. supervised the experiment. T.H.K., T.B. and A.F. drafted the manuscript, and all authors approved the final draft.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Andre Franke.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Methods, Supplementary Note, Supplementary Tables 1–6 and Supplementary Figures 1–11

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DOI

https://doi.org/10.1038/ng.553

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