Genetics and stem cells

Genes linked to back condition

“A genetic breakthrough into the causes of an incurable spine condition could help tens of thousands of young people to avoid pain and disability,” reports The Independent .

The news story is based on a study that looked for genetic variations associated with the disease ankylosing spondylitis, a type of chronic (long-term) arthritis that affects parts of the spine. Researchers carried out a genome-wide association study, looking at which genetic variations were more common in people with the condition than in those without it.

This study identified several new genetic variants associated with the disease. It also confirmed the associations in variants in six other locations found in previous studies. The researchers also began to look at which genes near to these variants may be playing a role. The next step will be to confirm which genes in these nine locations are playing a role in the disease.

Identifying genes that contribute to causing ankylosing spondylitis will help researchers to understand the biology of this disease better. This knowledge may in time suggest new approaches for treating the condition. However, this is not guaranteed, and it will not be a quick process because such advances will take time.

Where did the story come from?

The study was carried out by researchers from The Australo-Anglo-American Spondyloarthritis Consortium and the Wellcome Trust Case Control Consortium 2. Funding was provided by a variety of sources, including Arthritis Research UK, the Wellcome Trust and the Oxford Comprehensive Biomedical Research Centre. The study was published in the peer-reviewed scientific journal Nature Genetics .

This story was covered in The Times and The Independent. Both articles delivered balanced coverage, but could have benefited from some guidance on how long it may take for these findings to develop into actual treatments.

What kind of research was this?

The aim of this genome-wide association study was to identify genes that are related to the condition ankylosing spondylitis, a type of chronic (long-term) arthritis that affects parts of the spine.

Ankylosing spondylitis has a strong genetic component, i.e. a person’s genetics determine to a large extent whether they have the condition. Exactly which genes play a role is not yet fully understood, although it has been associated with the HLA-B27 gene. This gene encodes a protein that is involved in promoting an immune system response. However, only 1-5% of people who carry the HLA-B27 gene develop ankylosing spondylitis, and there is strong evidence from studies of the distribution of the disease in the population to suggest that other genes are involved. This study aimed to identify some of these other genes.

What did the research involve?

The researchers analysed DNA from 1,787 people from Britain and Australia who had the condition (cases) and 4,800 controls of European ancestry. They looked at genetic variations across the DNA to determine whether there were differences between people who had the condition and those who didn’t. The researchers combined their findings with the findings of another similar study, the Australo-Anglo-American Spondyloarthritis Consortium, which looked for genetic assocations in 3,023 cases and 8,779 controls.

Finally, the researchers then tried to replicate their findings in another group of 2,111 affected and 4,483 unaffected individuals from Australia, Britain and Canada. This is a key step in determining whether the results are robust or not.

What were the basic results?

The researchers confirmed several genetic variations that previous studies had associated with the disease, near the genes HLA-B, ERAP1, IL23R, KIF21B or in areas on chromosome 2 or 21 where there were no known genes. In addition, the researchers identified variations in three new positions of the DNA, which showed very strong associations with ankylosing spondylitis. These variations were near to the genes RUNX3, LTBR-TNFRSF1A and IL12B. A further four variations were also found near to the genes PTGER4, TBKBP1, ANTXR2 and CARD9, which showed strong association.

The researchers examined what proteins are produced by some of the genes in the identified regions, and what they do in the body. They found that RUNX3 encodes a protein that is needed to form a certain type of immune cell that individuals with ankylosing spondylitis have less of. They also found that the gene PTGER4 encodes a protein that is thought to play a role in bone strengthening in response to stress (in ankylosing spondylitis new bone is formed inappropriately, causing the bones of the spine to fuse).

The researchers also investigated whether there were any interactions between genetic regions that were established as being associated with ankylosing spondylitis and the newly identified regions. They found that in people who carried the variation in the HLA-B27 gene, those who also carried the variation in ERAP1 were more likely to have ankylosing spondylitis. However, this association between the variation in ERAP1 and ankylosing spondylitis was not seen in people who did not carry HLA-B27.

The other newly identified genetic variations were associated with ankylosing spondylitis, independent of HLA-B27 status.

How did the researchers interpret the results?

The researchers conclude that their findings have increased the number of genetic locations that are convincingly associated with ankylosing spondylitis. Each location contains genes that appear to have biological functions that are feasibly connected to ankylosing spondylitis.


This was a well-performed study that identified a number of novel genetic variations associated with ankylosing spondylitis. Ideally, these results will be confirmed in other studies on different groups of cases and controls. The genetic variations identified in this type of study are not necessarily causing the disease themselves, but may lie near genes that affect the risk of having the disease. The researchers have identified genes near to these genetic variations that could feasibly be playing a role in ankylosing spondylitis, based on what is known about the disease. However, this will need to be established in future studies.

Identifying genes that contribute to causing ankylosing spondylitis will help researchers to understand better the biology of this disease. This knowledge may suggest new approaches to treating the condition. However, this is not guaranteed and will not be a quick process as such advances will take time.

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