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

Ellinghaus D, Jostins L, Spain SL, Cortes A, Bethune J, Han B, Rang Park Y, Raychaudhuri S, Pouget JG, Hübenthal M, Folseraas T, Wang Y, Esko T, Metspalu A, Westra H-J, Franke L, Pers TH ,Weersma RK, Collij V, D’Amato M, Halfvarson J, Boeck Jensen A, Lieb W, Degenhardt F, Forstner AJ, Hofmann AInternational IBD Genetics Consortium (IIBDGC)International Genetics of Ankylosing Spondylitis Consortium (IGAS)International PSC Study Group (IPSCSG)Genetic Analysis of Psoriasis Consortium (GAPC)Psoriasis Association Genetics Extension (PAGE); Schreiber S, Mrowietz U, Juran BD, Lazaridis KN, Brunak S, Dale AM, Trembath RC, Weidinger S, Weichenthal M, Ellinghaus E, Elder JT , Barker JNWN, Andreassen OA, McGovern DP, Karlsen TH, Barrett JC, Parkes M, Brown MA, Franke A
Year of publication:








Journal (long):

Nature genetics

Journal (short):

Nat Genet

Impact factor:



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.

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