Study finds genetic link to common form of liver cirrhosis

UK scientists have found 15 new genetic regions that may affect a person's risk of developing primary biliary cirrhosis (PBC), a chronic form of liver disease. The research, carried out as part of the Wellcome Trust Case Control Consortium Three (WTCCC3) project, compared the genomes of 2,500 people with the disease with DNA from more than 7,500 healthy people. The researchers found 22 regions of the genome that differed significantly between healthy people and people with the disease, 15 which had not previously been identified.

Many of these new regions contained genes involved in regulating the immune system. One of these, called the NF-κB pathway, was not previously associated with primary biliary cirrhosis. The pathway is known to play a role in autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and asthma.

'By scrutinising the genes within these regions we were able to identify biological pathways that appear to underpin the disease, thus prioritising these for future research and highlighting their potential for therapeutic intervention', said one of the lead authors Dr Carl Anderson from the UK's Wellcome Trust Sanger Institute.

Primary biliary cirrhosis affects about 35 out of every 100,000 adults and there are no proven treatments. People with the disease suffer irritation and swelling of the bile ducts of the liver. This in turn blocks the flow of bile, which aids digestion. The blockage damages liver cells and causes irreparable scarring, known as cirrhosis. Although it is known that primary biliary cirrhosis is an autoimmune disease - where the body attacks its own cells - its underlying biological causes are not well understood.

'The publication of this paper is no routine academic matter for people with primary biliary cirrhosis', said Collette Thain, Chief Executive of the PBC Foundation.

As a sufferer herself, she added: 'For us, it means hope - one step towards understanding how best to treat and cure. It is a testament to the perseverance and ingenuity of all the scientists who worked on this project. But because this was a collaborative project, part funded by the PBC Foundation and directly involving patients, it is also an example of how people with conditions like primary biliary cirrhosis can work together with scientists and physicians to find solutions'.

The WTCCC3, a collaboration of UK scientists and clinicians, uses genome-wide association studies (GWAS) to understand the genetics of several different diseases, including primary biliary cirrhosis, anorexia nervosa, and pre-eclampsia.

The study was published in the journal Nature Genetics.