Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci (original) (raw)

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Acknowledgements

The authors wish to thank all PSC cases and healthy controls for their participation. We also thank K. Cloppenborg-Schmidt, I. Urbach, I. Pauselis, T. Wesse, T. Henke, R. Vogler, B. Stade, T. Vennegerts, P.R. Berg, H.D. Sollid and B. Woldseth for expert technical help. We are grateful to M.K. Viken and M. Nothnagel for helpful discussions. We acknowledge B.A. Lie and the Norwegian Bone Marrow Donor Registry at Oslo University Hospital, Rikshospitalet for contributing the healthy Norwegian control population. We acknowledge F. Braun, W. Kreisel, T. Berg and R. Günther for contributing German PSC cases. We acknowledge A. Strasser for generating and kindly providing the _Bcl2l11_−/− mouse model. We greatly acknowledge A. Kaser for managing the _Bcl2l11_−/− liver histology assessment and for helpful discussions on the functional implications of all findings. The study was supported by The Norwegian PSC research center, the German Federal Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN), the PopGen biobank, the Integrated Research and Treatment Center–Transplantation (reference number: 01EO0802), the Palumbo Charitable Trust, the Musette and Allen Morgan Jr. Foundation for the Study of PSC, PSC Partners Seeking a Cure and the Mayo Clinic College of Medicine. The project received infrastructure support through the Norwegian Functional Genomics Programme (FUGE) through the 'CIGENE' platform, the Research Computing Services at the University of Oslo and the Deutsche Forschungsgemeinschaft (DFG) excellence cluster 'Inflammation at Interfaces'. The Kooperative Gesundheitsforschung in der Region Augsburg (KORA) research platform was initiated and financed by the Helmholtz Center Munich, German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823). This research was also supported within the Munich Center of Health Sciences (MC Health) as part of Ludwig-Maximilians-Universität (LMU) innovativ.

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Author notes

1. Espen Melum and Andre Franke: These authors contributed equally to this work.
2. Stefan Schreiber and Tom H Karlsen: These authors jointly directed this work.

Authors and Affiliations

1. Norwegian PSC Research Center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway
   Espen Melum, Kirsten Muri Boberg, Johannes Roksund Hov, Kristian Holm, Erik Schrumpf & Tom H Karlsen
2. Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
   Espen Melum & Johannes Roksund Hov
3. Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
   Andre Franke, Eva Ellinghaus, Tobias Balschun, David Ellinghaus, Michael Wittig & Stefan Schreiber
4. 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
   Christoph Schramm & Martina Sterneck
5. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
   Tobias J Weismüller, Jochen Wedemeyer & Michael P Manns
6. Integrated Research and Treatment Center-Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany
   Tobias J Weismüller, Jochen Wedemeyer & Michael P Manns
7. Department of Medicine, University Hospital of Heidelberg, Heidelberg, Germany
   Daniel Nils Gotthardt, Peter Sauer & Adolf Stiehl
8. Academic Teaching Hospital Feldkirch, Feldkirch, Austria
   Felix A Offner
9. Division of Gastroenterology and Hepatology, Center for Basic Research in Digestive Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
   Brian D Juran & Konstantinos N Lazaridis
10. Centre for Molecular Biology and Neuroscience (CMBN) and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
    Jon K Laerdahl
11. Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria
    Verena Labi & Andreas Villunger
12. Department of Internal Medicine, Section of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden
    Einar Björnsson & Björn Lindkvist
13. Department of Gastroenterology and Hepatology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands
    Rinse K Weersma
14. Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium
    Liesbet Henckaerts & Severine Vermeire
15. 1st Department of Medicine, University of Mainz, Mainz, Germany
    Andreas Teufel
16. Department of Medicine 2, Grosshadern, University of Munich, Munich, Germany
    Christian Rust
17. Department of Gastroenterology and Hepatology, Karolinska University Hospital Huddinge, Stockholm, Sweden
    Annika Bergquist
18. Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Euijung Ryu
19. Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    Robert J Porte
20. Institute of Epidemiology, Helmholtz Centre Munich, German Research Center for Environmental Health, Neuherberg, Germany
    Christian Gieger & H-Erich Wichmann
21. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
    H-Erich Wichmann
22. Klinikum Grosshadern, Munich, Germany
    H-Erich Wichmann
23. Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Pieter Stokkers, Cyriel Y Ponsioen & Ulrich Beuers
24. Department of Human Genetics, University Hospital of Heidelberg, Heidelberg, Germany
    Heiko Runz
25. Department of Genetics, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands
    Cisca Wijmenga
26. Department for General Internal Medicine, Christian-Albrechts-University, Kiel, Germany
    Stefan Schreiber

Authors

1. Espen Melum
2. Andre Franke
3. Christoph Schramm
4. Tobias J Weismüller
5. Daniel Nils Gotthardt
6. Felix A Offner
7. Brian D Juran
8. Jon K Laerdahl
9. Verena Labi
10. Einar Björnsson
11. Rinse K Weersma
12. Liesbet Henckaerts
13. Andreas Teufel
14. Christian Rust
15. Eva Ellinghaus
16. Tobias Balschun
17. Kirsten Muri Boberg
18. David Ellinghaus
19. Annika Bergquist
20. Peter Sauer
21. Euijung Ryu
22. Johannes Roksund Hov
23. Jochen Wedemeyer
24. Björn Lindkvist
25. Michael Wittig
26. Robert J Porte
27. Kristian Holm
28. Christian Gieger
29. H-Erich Wichmann
30. Pieter Stokkers
31. Cyriel Y Ponsioen
32. Heiko Runz
33. Adolf Stiehl
34. Cisca Wijmenga
35. Martina Sterneck
36. Severine Vermeire
37. Ulrich Beuers
38. Andreas Villunger
39. Erik Schrumpf
40. Konstantinos N Lazaridis
41. Michael P Manns
42. Stefan Schreiber
43. Tom H Karlsen

Contributions

E.M. performed data analysis. A.F. and T.H.K. supervised data analysis and coordinated project contributions. E.E., T.B., D.E., J.R.H. and E.R. helped with data analysis. F.A.O., V.L. and A.V. performed the _Bcl2l11_−/− animal work and liver histology assessments. J.K.L. performed in silico analysis of chromosome 2q13 transcripts. M.W. and K.H. were responsible for in-house conversion and database management of genome-wide association study data. C.S., T.J.W., D.N.G., B.D.J., E.B., R.K.W., L.H., A.T., C.R., K.M.B., C.G., H.-E.W., A.B., P. Sauer, J.W., B.L., R.J.P., P. Stokkers, C.Y.P., H.R., A.S., C.W., M.S., S.V., U.B., E.S., K.N.L., M.P.M. and S.S. provided the case populations and healthy controls. S.S., A.F., T.H.K. and E.M. designed the experiment. E.M. and T.H.K. drafted the manuscript. All authors revised the manuscript and approved of the final version.

Corresponding author

Correspondence toTom H Karlsen.

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Competing interests

The authors declare no competing financial interests.

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Melum, E., Franke, A., Schramm, C. et al. Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.Nat Genet 43, 17–19 (2011). https://doi.org/10.1038/ng.728

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• Received: 20 June 2010
• Accepted: 16 November 2010
• Published: 12 December 2010
• Issue date: January 2011
• DOI: https://doi.org/10.1038/ng.728