Extraintestinal manifestations and complications in inflammatory bowel disease: from shared genetics to shared biological pathways.

Abstract:

BACKGROUND:The clinical presentation of the inflammatory bowel diseases (IBD) is extremely heterogenous and is characterized by various extraintestinal manifestations and complications (EIM). Increasing genetic insight for IBD and EIM shows multiple shared susceptibility loci. We hypothesize that, next to these overlapping genetic risk loci, distinct disease pathways are shared between IBD and EIM. METHODS:The overlapping genetic risk loci for IBD and its EIM were searched in literature. We assessed shared disease pathways by performing an extensive pathway analysis by protein-protein interaction and cotranscriptional analysis, using both publicly available and newly developed databases. RESULTS:Reliable genetic data were available for primary sclerosing cholangitis, ankylosing spondylitis, decreased bone mineral density, colorectal carcinoma, gallstones, kidney stones, and deep venous thrombosis. We found an extensive overlap in genetic risk loci, especially for IBD and primary sclerosing cholangitis and ankylosing spondylitis. We identified 370 protein-protein interactions, of which 108 are statistically specific. We identified 446 statistically specific cotranscribed gene pairs. The interactions are shown to cluster in specific biological pathways. CONCLUSIONS:We show that the pathogenetic overlap between IBD and its EIM extends beyond shared risk genes to distinctive shared biological pathways. We define genetic background as a risk factor for IBD-EIM alongside known mechanisms such as malabsorption and medication. Clustering patients based on distinctive pathways may enable stratification of patients to predict development of EIM.

journal_name

Inflamm Bowel Dis

authors

van Sommeren S,Janse M,Karjalainen J,Fehrmann R,Franke L,Fu J,Weersma RK

doi

10.1097/MIB.0000000000000032

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

987-94

issue

6

eissn

1078-0998

issn

1536-4844

journal_volume

20

pub_type

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