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How Does Genotype Influence Disease Phenotype in Inflammatory Bowel Disease?

Ananthakrishnan, Ashwin N. MD, MPH*,†; Xavier, Ramnik J. MD, PhD*,†,‡,§

doi: 10.1097/MIB.0b013e318281f5c5
Translational Review Article

Abstract: Inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) are chronic immunologically mediated diseases of the gut. Advances in genetics have revolutionized our understanding of the pathogenesis of these conditions with 163 risk loci identified, encompassing a variety of immunologic functions. There is substantial heterogeneity in the natural history of these diseases with respect to disease onset, course, and progression to complications. There are also significant variations in response to therapies and susceptibility to therapy-related and disease-related complications. An important need in the field is to identify predictors of disease course, complications, and likelihood of response and adverse events to allow for targeted therapeutic decision making. The genotype of an individual in constant and non-modifiable, and thus could potentially fulfill the role of important predictors of these outcomes. In this review, we discuss the existing literature on the prediction of various disease phenotypes in Crohn’s disease and ulcerative colitis using underlying genotype. We also identify gaps in the literature and suggest future directions for research. There is need for large, multi-institutional, and international collaborative consortia with efficient and detailed cohort accrual, phenotypic definition, genotyping, and dynamic assessments of external (e.g., diet) and internal (microbiome) environment to allow us to progress toward personalized and precision medicine in the management of these complex diseases.

Article first published online 2 may 2013

*Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts;

Harvard Medical School, Boston, Massachusetts;

Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts; and

§Broad Institute of Harvard University, Massachusetts Institute of Technology, Cambridge, Massachusetts.

Reprints: Ashwin N. Ananthakrishnan, MD, MPH, Massachusetts General Hospital Crohn’s and Colitis Center, 165 Cambridge Street, 9th Floor, Boston, MA 02114 (e-mail:

Supported by the National Institutes of Health (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. A. N. Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). R. J. Xavier is supported by grants U01 DK062432 & R01 DK064869 from the National Institutes of Health.

The authors have no conflicts of interest to disclose.

Received November 06, 2012

Accepted November 26, 2012

© Crohn's & Colitis Foundation of America, Inc.
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