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A study by Nuffield Department of Medicine’s Wellcome Centre for Human Genetics, and collaborating researchers have uncovered the genetic signals that cause ankylosing spondylitis, a type of spinal arthritis.

In their study from Cell Genomics, the researchers from Wellcome Centre for Human Genetics, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, and the Data Science, Population Analytics, Janssen R&D describe how they compared blood cells from patients with the condition to healthy individuals in order to understand the underlying causes of ankylosing spondylitis.

Ankylosing spondylitis is a common form of arthritis affecting 200,000 people in the UK, causing severe pain and leading to debilitating spinal fusion due to excess bone formation. Up to 40% of ankylosing spondylitis patients have unacceptable side effects or inadequate response to current treatments, which include powerful immune-targeting ‘biologic’ therapies. The results from this new study offer new hope to patients and their families as they pave the way for the development of more advanced treatment options that might cure the disease.

We have known for more than 40 years that ankylosing spondylitis has a strong genetic predisposition, and previous work by this group and others has identified more than 100 variants in the genetic code that increase the risk of an individual developing the condition. Even though ankylosing spondylitis is a disease of the spine, it is actually caused by certain types of immune cells becoming overactive. This study aims to address how small changes in DNA sequence alter the way DNA is packaged, altering which genes are operating and causing this unwanted immune activity.

Dr Carla Cohen, Computational Biologist from NDM’s Wellcome Centre for Human Genetics said: “This study represents an important breakthrough of linking genetic information to disease mechanism. Our findings have critical implications for the development of new treatments in ankylosing spondylitis, as well as other related immune-based conditions such as psoriasis and inflammatory bowel disease”.

The study involved applying different methods for studying gene expression and mechanisms regulating that expression in primary blood cells from patients with ankylosing spondylitis and healthy controls, linking this with genetic variants previously associated with the disease.

Prof Julian Knight, Professor of Genomic Medicine, at the Wellcome Centre for Human Genetics, said: “This is a highly collaborative study concluding many years of research that provides a route map to link genetic association to the mechanism and potential drug targets in ankylosing spondylitis using functional genomics. The work further underlines how we need to look for functional effects of disease-associated genetic variants in the appropriate cellular and disease contexts, in ankylosing spondylitis and other immune-mediated conditions.”

This study was supported by the NIHR Oxford Biomedical Research Centre.