Document Type
Article
Publication Date
4-19-2017
Identifier
PMCID: PMC5396125 DOI: 10.1038/srep46454
Abstract
Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort (BIRC2 p = 0.004, NFKB1 p = 0.005, NOD2 p = 0.029 and SUGT1 p = 0.047). Statistical significance was replicated for BIRC2 (p = 0.041) and NOD2 (p = 0.045) in an independent validation cohort. A gene based test on the combined discovery and replication cohort confirmed association for BIRC2 (p = 0.030). We successfully applied burden of mutation testing that jointly assesses common and rare variants, identifying two previously implicated genes (NFKB1 and NOD2) and confirmed a possible role in disease risk in a previously unreported gene (BIRC2). The identification of this novel gene provides a wider role for the inhibitor of apoptosis gene family in IBD pathogenesis.
Journal Title
Sci Rep
Volume
7
First Page
46454
Last Page
46454
MeSH Keywords
Adolescent; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Exome; Female; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Infant; Inflammatory Bowel Diseases; Inhibitor of Apoptosis Proteins; Male; Models, Biological; Mutation; Nod Signaling Adaptor Proteins; Nod2 Signaling Adaptor Protein; Signal Transduction; Ubiquitin-Protein Ligases; Whole Exome Sequencing
Keywords
IBD; children
Recommended Citation
Andreoletti G, Shakhnovich V, Christenson K, et al. Exome Analysis of Rare and Common Variants within the NOD Signaling Pathway. Sci Rep. 2017;7:46454. Published 2017 Apr 19. doi:10.1038/srep46454
Included in
Digestive System Diseases Commons, Gastroenterology Commons, Genetic Structures Commons, Pediatrics Commons
Comments
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Publisher's Link: https://www.nature.com/articles/srep46454