Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci

Trine Folseraas, Espen Melum, Philipp Rausch, Brian D. Juran, Eva Ellinghaus, Alexey Shiryaev, Jon K. Laerdahl, David Ellinghaus, Christoph Schramm, Tobias J. Weismueller, Daniel Nils Gotthard, Johannes Roksund Hov, Ole Petter Clausen, Rinse K. Weersma, Marcel Janse, Kirsten Muri Boberg, Einar Bjornsson, Hanns-Ulrich Marschall, Isabelle Cleynen, Philip RosenstielKristian Holm, Andreas Teufel, Christian Rust, Christian Gieger, H-Erich Wichmann, Annika Bergquist, Euijung Ryu, Cyriel Y. Ponsioen, Heiko Runz, Martina Sterneck, Severine Vermeire, Ulrich Beuers, Cisca Wijmenga, Erik Schrumpf, Michael P. Manns, Konstantinos N. Lazaridis, Stefan Schreiber, John F. Baines, Andre Franke, Tom H. Karlsen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

156 Citations (Scopus)


Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on,a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS).

Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing.

Results: Seventeen SNPs representing 12 distinct genetic loci achieved nominal significance (p(replication)

Conclusions: We identify multiple new PSC risk loci by extended analysis of a PSC GWAS. FUT2 genotype needs to be taken into account when assessing the influence of microbiota on biliary pathology in PSC. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)366-375
Number of pages10
JournalJournal of Hepatology
Issue number2
Publication statusPublished - Aug-2012


  • Primary sclerosing cholangitis
  • Genome-wide association study
  • Single nucleotide polymorphism
  • Immunogenetics
  • FUT2
  • GENE

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