Researchers have newly associated nine genetic regions with a rare autoimmune disease of the liver known as primary sclerosing cholangitis (PSC). This brings the total number of genetic regions associated with the disease to 16.
Approximately 70 per cent of people who suffer from PSC also suffer from IBD. The team showed that only half of the newly associated genetic regions were shared with inflammatory bowel disease (IBD). For the first time, this definitively proves that PSC, although genetically related to IBD, is a distinct disease.
PSC is a chronic, progressive disease of the bile ducts that channels bile from the liver into the intestines. It can cause inflammation of the bile ducts (cholangitis) and liver scarring that leads to liver cirrhosis and liver failure. There are no effective treatments available. Although PSC affects only one in 10,000 people, it is a leading cause of liver transplant surgery.
"Before our study, it was never quite clear whether PSC was a complication of IBD or a distinct disease in its own right," says Dr Carl Anderson, lead author from the Wellcome Trust Sanger Institute. "We have proven it to be a unique disease, and hope that our results will inform the development of more effective treatments, designed to target the biological pathways involved in causing the disease".
The work involved an international group of scientists from the International PSC study group recruiting patients from 13 countries within Europe and North America. Without this large collaborative effort it would not have been possible to obtain the large number of patient DNA samples necessary for the study.
The team used DNA genotyping technology to survey more thoroughly regions of the genome known to underlie other immune-related diseases to discover if they also play a role in PSC susceptibility.
In addition to the nine genetic regions newly associated, they also saw strong signals at three regions of the genome previously associated with the disease. Of these twelve genetic regions, six are also associated with IBD, while the six other regions showed little to no association in a recent large study of IBD.
"Using the Immunochip genotyping chip, we can pull apart the genetic relationships between these autoimmune diseases and begin to see not only their genetic similarities, but also the differences," says Jimmy Liu, PhD student and first author from the Wellcome Trust Sanger Institute. "As PSC is a rare disorder, sample collection is more difficult than for other, more common, autoimmune diseases. We hope that with more samples from patients, we'll be able to link more genetic regions to the disease, and it will become easier to identify underlying pathways that could act as therapeutic targets."
Three of the genetic regions associated with PSC fall within a single biological system that underlies variation in T cells, cells important to our immune response. One gene that controls this pathway, HDAC7, is known to be a key factor in immune tolerance and the new data strongly suggests exploring the possibility that drugs affecting HDAC7 function may serve as future therapeutics in PSC.
In an extended analysis, the team identified an additional 33 genetic regions that are also involved in several common immune-mediated conditions (celiac disease, Crohn's disease, ulcerative colitis, type 1 diabetes, rheumatoid arthritis, sarcoidosis and psoriasis). This analysis shows that PSC shares many genetic risk loci with other immune-mediated diseases and opens up the possibility for testing drugs known to be effective in genetically similar diseases for efficacy in PSC.
The next step for the team is to do a high-powered search throughout the entire genomes of PSC patients to find specific regions associated with PSC outside of the regions included on the Immunochip genotyping chip.
"This study has uncovered more about the genetics underlying PSC than any before it, but this is only the first step" says Dr Tom Hemming Karlsen, lead author from Oslo University Hospital, Norway. "We hope the ongoing scientific and clinical research being conducted through the International PSC study group will help improve the outlook for those currently suffering at the hands of this disease"
"Our study, which is the largest of its type for PSC, would not have been possible without the help of the patients with this rare disorder," adds Dr Hemming Karlsen.
Notes to Editors
Publication DetailsJimmy Z Liu, Johannes Roksund Hov, Trine Folseraas et al (2013) "Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis"
A full list of funding can be found in the paper
A full list of participating centres can be found in the paper
Selected WebsitesThe Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.
Aileen Sheehy | EurekAlert!
Flavins keep a handy helper in their pocket
25.04.2018 | University of Freiburg
Complete skin regeneration system of fish unraveled
24.04.2018 | Tokyo Institute of Technology
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
25.04.2018 | Physics and Astronomy
25.04.2018 | Physics and Astronomy
25.04.2018 | Information Technology