Ellinghaus, D., Jostins, L., Spain, S. L., Cortes, A., Bethune, J., Han, B., Park, Y. R., Raychaudhuri, S., Pouget, J. G., Hubenthal, M., Folseraas, T., Wang, Y. P., Esko, T., Metspalu, A., Westra, H. J., Franke, L., Pers, T. H., Weersma, R. K., Collij, V., D'Amato, M., Halfvarson, J., Jensen, A. B., Lieb, W., Degenhardt, F., Forstner, A. J., Hofmann, A., Schreiber, Stefan, Mrowietz, U., Juran, B. D., Lazaridis, K. N., Brunak, S., Dale, A. M., Trembath, R. C., Weidinger, S., Weichenthal, M., Ellinghaus, E., Elder, J. T., Barker, Jnwn, Andreassen, O. A., McGovern, D. P., Karlsen, T. H., Barrett, J. C., Parkes, M., Brown, M. A. and Franke, A. (2016) Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nature Genetics, 48 (5). 510-+. DOI 10.1038/ng.3528.

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Abstract

We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.

Document Type:	Article
Additional Information:	Times Cited: 9 Ellinghaus, David Jostins, Luke Spain, Sarah L. Cortes, Adrian Bethune, Joern Han, Buhm Park, Yu Rang Raychaudhuri, Soumya Pouget, Jennie G. Huebenthal, Matthias Folseraas, Trine Wang, Yunpeng Esko, Tonu Metspalu, Andres Westra, Harm-Jan Franke, Lude Pers, Tune H. Weersma, Rinse K. Collij, Valerie D'Amato, Mauro Halfvarson, Jonas Jensen, Anders Boeck Lieb, Wolfgang Degenhardt, Franziska Forstner, Andreas J. Hofmann, Andrea Schreiber, Stefan Mrowietz, Ulrich Juran, Brian D. Lazaridis, Konstantinos N. Brunak, Soren Dale, Anders M. Trembath, Richard C. Weidinger, Stephan Weichenthal, Michael Ellinghaus, Eva Elder, James T. Barker, Jonathan N. W. N. Andreassen, Ole A. McGovern, Dermot P. Karlsen, Tom H. Barrett, Jeffrey C. Parkes, Miles Brown, Matthew A. Franke, Andre
Research affiliation:	OceanRep > The Future Ocean - Cluster of Excellence Kiel University
Refereed:	Yes
Open Access Journal?:	No
Publisher:	Nature Research
Projects:	Future Ocean
Date Deposited:	20 Feb 2017 11:34
Last Modified:	22 May 2019 12:40
URI:	https://oceanrep.geomar.de/id/eprint/36074

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