Researchers Reveal Findings From Primary Sclerosing Cholangitis Study


A study drove researchers to find four previously unknown genetic risk locations for a liver disease that lacks effective medical treatment, primary sclerosing cholangitis. A December, 2016 article in Nature Genetics highlights the effort. This is currently the largest genome-wide association study of primary sclerosing cholangitis and takes a step toward providing breakthrough therapy for the unmet needs of primary sclerosing cholangitis patients.

Mayo Clinic’s Konstantinos Lazaridis, M.D., and Carl Anderson, Ph.D., of the Wellcome Trust Sanger Institute led the research, along with collaborators from six other U.S. medical centers and co-investigators from the U.K., Germany and Norway and collaborators from other European countries.

Primary sclerosing cholangitis affects 1 in 10,000 people, with about 75 percent developing inflammatory bowel disease (IBD). However, only 5 to 7 percent of those affected by pre-existing IBD alone later develop primary sclerosing cholangitis.

Analysts compared the genetic information of almost 5,000 people with primary sclerosing cholangitis against a control population of nearly 20,000 individuals, the specimens of which were provided by patients from the U.S. and Europe.

“Considering the rarity of those affected by primary sclerosing cholangitis, the contribution of specimens by multiple centers across the globe allowed us to view the genetic comparisons of this disease in a much bigger picture. This is a testament of trust from the primary sclerosing cholangitis patients to this investigative team to whom we are grateful. We feel a strong spirit of collaboration with the International PSC Study Group and all the medical centers involved.” Dr. Lazaridis stated.

Working with this information, analysts discovered four new markers of primary sclerosing cholangitis risk on the human genome. That brings the total number of known predisposing locations to twenty. One of the four new reported loci is expected to lower the protein expression of UBASH3A, a molecule that regulates T-cell signaling and correlates with lowering the risk of primary sclerosing cholangitis. Dr. Lazaridis says this molecule should be studied further as a target of treatment for the disorder.

The research also allowed for clearer estimations as to how primary sclerosing cholangitis and IBD may share genetic risk factors. Lazaridis stated, “The immense scale of this genetic study allowed us to analyze for the first time the complex genetic relationship between primary sclerosing cholangitis and IBD. Additional scientific efforts for genome sequencing of primary sclerosing cholangitis patients will give us more opportunities to find the specific genetic underpinnings that contributing to the risk of primary sclerosing cholangitis and to explain what makes the correlation between primary sclerosing cholangitis and IBD.”


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