Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci
By David Ellinghaus, L. Jostins, S. Spain, A. Cortes, J. Bethune, B. Han, Yu Rang Park, Soumya Raychaudhuri, J. Pouget, M. Hübenthal and 35 more. Nature Genetics, 2016
719 citations recorded by the source corpus.
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.
View Paper: https://www.semanticscholar.org/paper/372a076554a5ec1f9e595ef356670468d66cfa6a
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Genetics
- Jian Yang
- Naomi R. Wray
- Peter M. Visscher
- Mark I. McCarthy
- Frank Dudbridge
- Alkes L Price
- Michael E. Goddard
- Matthew Stephens
Citations in the corpus
- Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease (2016, background): “[8]Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK”
- 10 Years of GWAS Discovery: Biology, Function, and Translation. (2017, background): “12 The American Journal of Human Genetics 101, 5–22, July 6, 2017 613806), and psoriasis identified without any further genotyping 30 new loci at genome-wide significance.(24) Transethnic studies have demonstrated substantial genetic overlap between ethnically remote populations; for example, geneti”