Basic—Liver, Pancreas, and Biliary TractGenome-Wide Association Analysis in Primary Sclerosing Cholangitis
Section snippets
Study Panels
The diagnosis of PSC was based on accepted criteria and typical findings on cholangiography.1 In total, 285 PSC patients (74% male) and 298 healthy controls (59% male) from Norway (discovery panel), 137 PSC patients (67% male) and 368 healthy controls (70% male) from Norway and Sweden (verification panel 1), 229 PSC patients (63% male) and 735 healthy controls (54% male) from Belgium and The Netherlands (verification panel 2), and 400 PSC patients (69% male) and 1832 healthy controls (41% male)
Results
Population stratification in the discovery panel was found to be negligible with a genomic inflation factor of 1.03 (Supplementary Figure 2). A multidimensional scaling plot of genetic relatedness across ethnicities also showed that our samples segregated together with individuals of European origin in the HapMap samples (Supplementary Figure 3).
Discussion
By combining a genome-wide association study design with gene-centric investigations based on previous findings in UC, our study verified the importance of susceptibility variants within the HLA complex in PSC and provided novel evidence for the presence of at least 3 non-HLA susceptibility loci.
Given the genetic complexity of any HLA association, biological insight may be derived more easily from the 3 non-HLA PSC loci. However, similar for most susceptibility loci detected in genome-wide
Acknowledgments
The authors wish to thank all primary sclerosing cholangitis patients and healthy controls for their participation. The authors also thank Tanja Wesse, Tanja Henke, Rainer Vogler, Katja Cloppenborg-Schmidt, Eva Buchert, Hege Dahlen Sollid, and Bente Woldseth for expert technical help. Professor Dr Thomas Wienker and Dr Michael Steffens (IMBIE, University of Bonn) are acknowledged for performing the quality control of the genome-wide single nucleotide polymorphism data set. The authors are
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Conflicts of interest The authors disclose no conflicts.
Funding The study was supported by the German Ministry of Education and Research (BMBF) through the National Genome Research Network and the PopGen biobank (www.popgen.de). The project received infrastructure support through the DFG excellence cluster “Inflammation at Interfaces” (www.inflammation-at-interfaces.de) and the Norwegian PSC research center (www.rikshospitalet.no/nopsc).