American College of Rheumatology Annual Meeting

American College of Rheumatology Annual Meeting

October 21, 2018
2 min read

Genetic risk score effective, less costly alternative to MRI in AS diagnosis

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Zhixiu Li

CHICAGO — Genetic risk score has a high discriminatory capacity, performs at least as well as MRI — while being far less expensive — and could be of clinical use in the early diagnosis of ankylosing spondylitis, according to data presented at the ACR/ARHP 2018 Annual Meeting.

“The diagnosis of ankylosing spondylitis is delayed on average by 8 to 10 years after the onset of symptoms,” Zhixiu Li, PhD, of the Queensland University of Technology, told Healio Rheumatology. “There is increasing evidence showing that early intervention can lead to better outcomes for AS patients. In this study we have developed and tested an AS polygenic risk score to assist in early diagnosis and to identify subjects at high risk of developing AS with approximately 37,000 samples. Our AS polygenic risk score uses the findings of tests for thousands of genetic variants to better capture the genetic susceptibility.”

To test the predictive value of polygenic risk scores in the early diagnosis of AS, compared with MRI and human leukocyte antigen (HLA) B27, Li and colleagues recruited two cohorts. The first, based on European samples, included 7,742 patients with AS and 14,542 control participants. The other cohort, based on East Asian samples, included 6,001 patients with AS and 4,943 control individuals. The researchers defined AS using the Modified New York Criteria, and all the samples were genotyped using Illumina CoreExome microarrays involving approximately 270,000 single nucleotide polymorphisms after quality control.

Genetic risk score has a high discriminatory capacity, performs at least as well as MRI in the early diagnosis of ankylosing spondylitis, according to data presented at the ACR/ARHP 2018 Annual Meeting.
Source: Shutterstock

The European group’s genetic risk score included 3,947 SNPs, while the East Asian cohort’s GRS involved 8,659 single nucleotide polymorphisms. The researchers performed a 10-fold cross-validation in the originator population. They also tested in Turkish — with 873 patients and 961 controls individuals — and Iranian — 430 patients and 761 control participants — case-control cohorts. Risk scores were calculated using the adaptive MultiBLUP algorithm. The researchers tested discriminatory capacity by receiver operating characteristic analysis, reported as area under the curve (AUC), with sensitivity and specificity reported at the best Matthews correlation coefficient.

According to Li, the AUC for the European genetic risk score was 0.92, with 83% sensitivity and 92% specificity, compared with 0.87 for HLA-B27 status (P = 2.4 x 10-10). Among the East Asian participants, the AUC was 0.95, with 91% sensitivity and 95% specificity. The risk score among patients with AS was significantly higher than that of the control individuals in both groups (P < 2.2 x 10-15).


Both the European and East Asian models demonstrated moderate discriminant capacity in other ethnic groups, including the Turkish and Iranian cohorts. In the European model, the AUCs were 0.85 for the Turkish group, 0.85 for the Iranian cohort and 0.78 for the East Asian group. In the East Asian model, the AUCs were 0.84, 0.87 and 0.88 for the Turkish, Iranian and European groups respectively.

“AS polygenic risk score has a high discriminatory capacity and could be clinically useful as an early diagnostic tool at lower cost than MRI,” Li said. “In addition, it may allow the identification of high-risk groups for early intervention or prevention studies. AS polygenic risk score could also be applied to patients with arthritic symptoms, but do not have a clear diagnosis to assist rheumatologists to make a diagnosis.” – by Jason Laday

Disclosure: Li reports no relevant financial disclosures. Please see the full study for additional authors’ disclosures.


Li Z. Abstract 835. Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.