Polygenic risk score can predict children's risk of developing scoliosis: Study
Japan: The researchers from Japan have developed and validated a genetic risk score for predicting the onset and severity of adolescent idiopathic scoliosis (AIS) -- the most common type of scoliosis in adolescents. The use of the score may help clinicians to identify children at risk of developing AIS who could benefit from preventive therapies.
"We found that a risk score based on genome-wide association study data could predict not only susceptibility to AIS, but also its severity. We hope our findings will be useful for personalized medicine," the researchers reported in the Journal of Bone and Mineral Research.
AIS is a common disease that causes spinal deformities in as many as 3% of youth. There is an immediate need for developing a method that can accurately detect the onset and progression of AIS. Because AIS has a high heritability of 87.5%, prediction of its onset and progression based on genetic data is a promising option. The researchers showed the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS.
Chikashi Terao, Chikashi Terao, the RIKEN Center for Integrative Medical Sciences, Japan, and colleagues used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, PRS was applied to a test data set.
Key findings of the study include:
- By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10−40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622).
- The decile with the highest PRS showed an odds ratio of as high as 3.36 to develop AIS compared with the fifth in decile.
- The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054), potentiating clinical use of the prediction model.
- The researchers found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6).
- The AIS PRS demonstrated a significant association with CA.
"These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery," concluded the authors.
June is Scoliosis Awareness Month.
The study titled, "Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use," is published in the Journal of Bone and Mineral Research.