Inflammatory Bowel Disease-Environmental Modification and Genetic Determinants

Subra Kugathasan, Devendra Amre

Research output: Contribution to journalReview articlepeer-review

Abstract

Complex disease such as IBD is controlled by multiple risk factors that evolve and interact with each other In a genetically susceptible host, there are multiple processing steps controlled by the host and the environment, from environmental exposure to the clinical and biological expression of IBD-related phenotypes. It should be obvious to most people that if new genetic discoveries are to attain their potential promise in IBD, the barriers to relax the assumptions of genotype-by-environment interactions need immediate attention. The first design issue in studying a complex disorder such as IBD is to identify and characterize the right population. Investigators should recognize this problem rather than simply work with convenient samples. For various reasons, children with newly diagnosed IBD (incident cases) are suited ideally to carry out such investigations. Technical advances of the HapMap project and the promise of whole-genome association scans have been impressive, driving down the cost of SNP genotyping while driving up the quality and completeness of the data to a degree far exceeding initial expectations. There is no single optimal design that will identify genetic and environmental factors that contribute to IBD risk most efficiently. Disease-oriented investigators who think that just by genotyping their cohorts they will produce a clean genomic solution to identifying genetic risks have been misled. The pathogenesis of IBD almost certainly is mediated by a network of effects, meaning that neither genetic nor environmental agents are separate causes of the disease state, but instead their interactions determine the risk. Investigators aimed at clarifying these interactions ultimately will lead to a clearer understanding of the underlying mechanisms of IBD, which will provide insight for improved prevention and treatment.

Original languageEnglish (US)
Pages (from-to)727-749
Number of pages23
JournalPediatric clinics of North America
Volume53
Issue number4
DOIs
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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