Polygenic risk scores may help identify ankylosing spondylitis earlier and at a lower cost than current testing methods, according to Australian research presented at the 2018 ACR/ARHP Annual Meeting in Chicago.
The genetic risk score (GRS) uses thousands of genetic variants to better calculate genetic susceptibility to the condition than single tests such as HLA-B27.
And while MRI has a high sensitivity for active disease, the genetic risk score could be particularly useful in symptomatic patients at an earlier stage of their disease or in individuals with a family history.
Dr Zhixiu Li, a research fellow at the Queensland University of Technology’s Institute of Health and Biomedical Innovation told the limbic the potential for earlier identification and hence earlier intervention was exciting.
She said the typical delay between the onset of symptoms and a diagnosis was eight to 10 years.
“In early disease, MRI is the current gold standard for diagnosis, but it is very expensive, and many patients with early changes on an MRI scan don’t go on to get ankylosing spondylitis. Thus, we think genetic profiling may be informative, particularly in early disease, but also potentially prior to onset of symptoms.”
The international research team developed two polygenic GRS models – one based on European-descent samples including 7,742 patients and 14,542 controls; the second based on East Asian-descent samples including 6,001 AS patients and 4,943 controls.
The European GRS model has about 4,000 variants and the East-Asian model about 8,600. Validation was performed in the originator populations as well as two separate cohorts.
The European GRS model was found to have a discriminatory capacity (area under the curve) of 0.92 and 0.95 for the East Asian GRS model. These compare favourably to the discriminatory capacity of 0.87 for HLA-B27 alone and 0.9 for MRI.
“To put this into context, the predictive value of LDL cholesterol for myocardial infarction has been reported as 0.82.”
“Our findings show that GRS has high discriminatory capacity and could be of clinical utility in early diagnosis at lower cost than MRI,” Dr Li said.
“In addition, the GRS could also be applied to identify individuals with high risk of developing AS before major symptoms appear. It could also be applied to patients with arthritic symptoms, but without a clear diagnosis.”
“We think we can improve the GRS further, and are working on optimising it using different statistical approaches. We also are looking at how GRS performs when combined with other clinical features or test results to further improve the power of detecting ankylosing spondylitis patients.”
While not commercially available yet, Dr Li said the GRS costs about US $50 compared to about AUS $75 for HLA-B27.