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Genetic Approaches to Functional Gastrointestinal Disorders.

Gastroenterology. 2010 Feb 19;

Authors: Saito YA, Mitra N, Mayer EA

Functional gastrointestinal disorders are complex symptom-based disorders without agreed upon biomarkers or pathophysiology. A better understanding of the genetic architecture of these disorders would help to better identify their complex biology, explain the common comorbidity with other disorders of persistent pain, mood and affect, and may make it possible to identify subgroups of patients who respond to customized therapies. In contrast to monogenic diseases, polygenic diseases and traits are characterized by the contribution of common variants in a large number of genes, as well as environmental factors, to the vulnerability of an individual. Family and twin studies have clearly established a genetic component in irritable bowel syndrome (IBS). Although candidate gene studies have identified a few gene polymorphisms which may be correlated with the syndrome, small sample size, lack of reproducibility in large data sets, and the unreliability of the clinical phenotype require caution when extrapolating to a major role of any of the reported polymorphisms in IBS pathophysiology. Future progress in this area will require better characterization of intermediate phenotypes with large effect size for the clinical phenotype, consideration of gene-gene, environment-gene, and sex-gene interactions, as well as genome-wide association, and whole genome sequencing approaches in large datasets.

PMID: 20176021 [PubMed - as supplied by publisher]

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