Can G-PROB Improve Diagnosis?
The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.
Dr. Liao
Dr. Katherine Liao
This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?
A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.
Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.
“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.
Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued.
“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
Future of Genetics in Rheumatology
An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.
There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.
“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.
Brown added that genetic testing is already used to make rheumatology diagnoses.
“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.
While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.
“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”
Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.
A version of this article appeared on Medscape.com.