Background: Over the last 2 decades, there has been an ever-expanding catalog of genetic variants implicated in inflammatory bowel disease (IBD) through genome-wide association studies and next generation sequencing. In this article, we highlight the remarkable developments in understanding the genetic and immunological basis of IBD. The main objective of the study was to perform a systematic review of published literature detailing functional/ immunological studies in patients known to harbor genetic variations in the implicated genes. Methods: A panel of 71 candidate genes implicated in IBD was prioritized using 5 network connectivity in silico methods. An electronic search using MEDLINE and EMBASE from 1996 to February 2014 for each of the selected genes was conducted. Only studies describing genotyped IBD cohorts with concurrent in vivo functional studies were included. Results: Between the reviewers, a total of 35,142 potentially eligible publications were identified. Only 8 genes had publications meeting the inclusion criteria. A total of 67 studies were identified across the selected genes. The NOD2 gene had the most number with 41 studies followed by IL-10 with 11 eligible studies. A meta-analysis was not practical given the heterogeneity of the study design and the number of implicated genes with diverse immunological and physiological functions. Conclusions: There is a clear lack of functional studies in humans to assess the in vivo impact of the various genetic variants implicated. A collaborative approach merging genomics and functional studies will help to unravel the obscure mechanisms involved in IBD. (Inflamm Bowel Dis 2014;20:1813–1819)
