Genes and functional GI disorders: from casual to causal relationship

Background The functional gastrointestinal disorders (FGID), and in particular irritable bowel syndrome (IBS), pose a considerable burden on health care and society, and negatively impact quality of life. These are common conditions of unknown etiology, and symptom-based criteria are currently the sole nosological tools for their clinical classification. Major insight into FGID pathophysiology is therefore needed and, in recent years, increasing hope has been put on genetic research for the identification of causative pathways. This is more advanced in IBS compared with other FGID, but it has still provided often indecipherable results and no unequivocal evidence of a pathogenetic role for any particular gene. Although thousands of genetic variants have been undoubtedly linked to human disease in hundreds of genome-wide association studies (GWAS), no similar effort has yet even been attempted in FGID. If meaningful, robust, and reproducible results are to be obtained for IBS and other FGID, we must shift gear and adopt these powerful hypothesis-free approaches through concerted actions and allocation of adequate resources. Provided these are in place, the major challenge will be, inevitably, the choice of the target phenotype(s) beyond a descriptive symptom-based classification. Purpose In view of these much awaited developments, salient results and difficulties inherent to IBS gene discovery are briefly summarized here.