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Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci


Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4–7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10−16 and P = 4.1 × 10−8, respectively).

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Figure 1: Association results at the MST1 and BCL2L11 loci.


  1. Broomé, U. & Bergquist, A. Semin. Liver Dis. 26, 31–41 (2006).

    Article  Google Scholar 

  2. Karlsen, T.H. et al. Gastroenterology 138, 1102–1111 (2010).

    Article  Google Scholar 

  3. Zhernakova, A., van Diemen, C.C. & Wijmenga, C. Nat. Rev. Genet. 10, 43–55 (2009).

    CAS  Article  Google Scholar 

  4. Bergquist, A. et al. Clin. Gastroenterol. Hepatol. 6, 939–943 (2008).

    Article  Google Scholar 

  5. Karlsen, T.H., Melum, E. & Franke, A. Hepatology 51, 1833–1842 (2010).

    CAS  Article  Google Scholar 

  6. Price, A.L. et al. Nat. Genet. 38, 904–909 (2006).

    CAS  Article  Google Scholar 

  7. Goyette, P. et al. Mucosal Immunol. 1, 131–138 (2008).

    CAS  Article  Google Scholar 

  8. Strasser, A. Nat. Rev. Immunol. 5, 189–200 (2005).

    CAS  Article  Google Scholar 

  9. Hsu, W. et al. Hepatology 49, 133–140 (2009).

    CAS  Article  Google Scholar 

  10. Hirschfield, G.M. et al. N. Engl. J. Med. 360, 2544–2555 (2009).

    CAS  Article  Google Scholar 

Download references


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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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.

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Correspondence to Tom H Karlsen.

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The authors declare no competing financial interests.

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Supplementary Tables 1 and 2, Supplementary Figures 1–5 and Supplementary Methods (PDF 3590 kb)

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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).

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