Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

Ellinghaus, David, Jostins, Luke, Spain, Sarah L., Cortes, Adrian, Bethune, Joern, Han, Buhm, Park, Yu Rang, Raychaudhuri, Soumya, Pouget, Jennie G., Hubenthal, Matthias, Folseraas, Trine, Wang, Yupeng, 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, Kostantinos 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. and Franke, Andre (2016) Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nature Genetics, 48 5: 510-518. doi:10.1038/ng.3528

Author Ellinghaus, David
Jostins, Luke
Spain, Sarah L.
Cortes, Adrian
Bethune, Joern
Han, Buhm
Park, Yu Rang
Raychaudhuri, Soumya
Pouget, Jennie G.
Hubenthal, Matthias
Folseraas, Trine
Wang, Yupeng
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, Kostantinos 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
Title Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1546-1718
Publication date 2016-05-01
Year available 2016
Sub-type Article (original research)
DOI 10.1038/ng.3528
Open Access Status Not yet assessed
Volume 48
Issue 5
Start page 510
End page 518
Total pages 9
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Subject 1311 Genetics
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.
Keyword Genome-wide association studies (GWAS)
Disease-specific patterns
Chronic inflammatory diseases
High-density genotype data
Complex pleiotropy
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 2013097
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
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