Reviews in Basic and Clinical GastroenterologyGenetic Approaches to Functional Gastrointestinal Disorders
Section snippets
Family and Twin Studies
Familial aggregation has been reproducibly shown in several clinic-based studies of patients with IBS (Table 1), while family studies of other FGIDs are lacking. However, clustering of IBS in families does not necessarily implicate a genetic basis, but could also result from environmental exposures shared in a household, including diet or lifestyle behaviors, exposure to adverse life events within the family, learned cognitions about disease and illness behavior, or even shared exposure to
Candidate Gene Studies
Candidate gene studies are studies whereby investigators postulate that a specific gene, and typically a specific functional gene polymorphism that results in alterations in protein function or quantity, may play a role in disease pathophysiology. The most commonly used approach in IBS to date has been to search for correlations of a candidate gene polymorphism with the symptom-based phenotype IBS (Table 3). More recently, a few studies have aimed to identify correlations between gene
Genome-wide Association Studies and Whole Genome Sequencing
More than 100 genome-wide association studies have been conducted for a large number of human diseases, identifying hundreds of polymorphisms with influence on disease vulnerability.32 However, in most of these studies, one or two genes that had already been known were confirmed, while a large number of common gene variants found in these studies are responsible only for a small fraction of the genetic variation that we know from family and twin studies. It is likely that a large number of
Summary and Conclusions
Gene discovery for complex polygenic disorders such as FGIDs remains a priority but represents a vast challenge. The field, in particular the individual candidate gene hunting approach, has been hampered by use of discrete and narrow symptom-based definitions—focusing on one disorder such as IBS—instead of objective biological phenotypes. Future studies seeking to identify causal genetic loci for FGIDs will likely use a combination of approaches, with candidate gene as well as genome-wide
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Conflicts of interest The authors disclose no conflicts.