Massively parallel characterization of adolescent idiopathic scoliosis risk variants.

Massively parallel assays identified 92 regulatory variants linked to adolescent idiopathic scoliosis, including a key variant near ADGRG6 affecting cartilage regulation.

• Why it matters: Understanding the functional impact of genetic variants in AIS is crucial because most are in noncoding regions, and their roles in disease mechanisms remain unclear, hindering biomarker and therapy development.
• What they did: The study tested 1,664 variants in chondrocyte cell lines using reporter assays, revealing 92 with significant allele-specific activity, notably validating rs9496392 near ADGRG6 that disrupts transcription factor binding.
• The result: These findings establish a functional catalog of AIS-associated regulatory variants active in chondrocytes, advancing knowledge of gene regulation in AIS and supporting future biomarker and therapeutic research.