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P828 Network analysis of GWAS reveals differential top-ranked risk loci and proteins associated with the inflammatory bowel disease phenotypes

M. Gazouli*1, N. Dovrolis2, A. Franke3, G. Spyrou4, G. Kolios2

1Medical School, National and Kapodistrian University of Athens, Biology, Athens, Greece, 2Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece, 3Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Kiel, Germany, 4Bioinformatics ERA Chair, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

Background

Crohn’s disease (CD) and Ulcerative colitis (UC) are the two main entities of inflammatory bowel disease (IBD). Genome-wide association studies (GWAS) identified more than 200 risk loci in populations of predominantly European ancestry.

Methods

Here we report the GWAS study of IBD data from an extended cohort of 573 Greek IBD patients (364 C and 209 UC) and 445 controls. We implicate 89 loci in IBD risk. Additionally, through pathway-based analysis we identified distinct functional pathways associated with each of the two IBD forms and their phenotypes.

Results

For the majority of the IBD susceptibility loci, the direction and magnitude of effect are consistent in IBD cohorts. Pathway analysis to detect functional interactions was performed using the KEGG and Reactome databases via the Enrichr gene list enrichment analysis tool. Protein associations were subsequently analysed using the STRING functional enrichment association network platform, to create extended protein networks enriched with additions from various experimental, bibliographical and gene interaction databases. These phenotype-specific functional interaction networks, through centrality analysis, reveal well known IBD-related genes and their interactors.

Conclusion

We introduce a novel approach that ranks the associated proteins and signalling pathways by disease implication and provides new insights into IBD’s molecular background, highlighting targets of potential diagnostic and therapeutic value.