as their principle goal is to define defective biological pathways implicated in certain pathologies. Such an approach was recently published in the journal Gastroenterology and focused on primary sclerosing cholangitis, or PSC, a disease very closely related to IBD. PSC is a liver disease characterized by chronic inflammation with fibrosis and gradual destruction of the intra- and extrahepatic bile ducts. In 75% of cases, it is associated with UC. It is an important risk factor in the development of colon cancer (risk multiplied by 5) and, in the USA, is the 5^th most frequent reason for liver transplantation. The etiology of PSC is unknown and the demonstration of susceptibility genes potentially involved in this pathology could provide crucial information on the onset and development of the disease. Results obtained in different European cohorts show a strong association between certain genes coding for histocompatibility proteins and the risk of developing PSC. Three other chromosomal regions would appear to be associated with a higher risk of developing PSC, two of which had been previously identified during similar studies on UC. Nevertheless, this work did not enable precise identification of genes potentially involved in PSC, though it did point out several genes suspected to play an important role in bile metabolism and the inflammatory response. Moreover, among 15 susceptibility genes identified for UC, only two were found for PSC, confirming that the chronic intestinal inflammation associated with PSC presents clinical manifestations which are clearly distinct from those of the other IBD. This study, along with future functional studies of the genes identified here and which are suspected to be involved in PSC, should lead to a better understanding of the physiopathology of PSC. Nonetheless, this disease continues to remain a mystery, and new studies will be necessary in order to identify its causes and mechanisms.

Genome-Wide Association analysis in Primary Sclerosing Cholangitis, Tom H. Karlsen et al. Gastroenterology, 2010, article in press