Figure 2.

A polygenic burden of novel variants in ECM genes is associated with AIS and correlates with Ghent systemic feature scores and joint hypermobility (A) AIS cases have more non-synonymous variants in genes within the ‘Extracellular Matrix Structural Constituent’ GO-term compared with controls (Fisher's exact test P-value = 6 × 10⁻⁹). (B) AIS prevalence increases with every additional novel variant. The blue line represents the population prevalence of 3% for individuals with scoliosis Cobb angle >10°. (C) Ghent systemic feature score and Beighton hypermobility scores are higher in AIS cases with ≥2 novel variants in genes in the ‘Extracellular Matrix Structural Constituent’ GO-term compared with AIS cases with <2 novel variants. None of the individuals in the AIS cohort were diagnosed with any known connective tissue disorder, including Marfan syndrome, Ehlers–Danlos syndrome or Stickler syndrome.