The most common spinal deformity in adolescence, and a genetics that splits into two separate questions: who develops it at all, and — a different locus, from a different study — who develops the severe form that needs treatment.
Adolescent idiopathic scoliosis (AIS) is a sideways curvature of the spine that appears during the growth spurt of adolescence, with no known cause — "idiopathic" means exactly that, a diagnosis of exclusion once other causes are ruled out. It is the most common spinal deformity, affecting roughly 2% of adolescents worldwide, most often girls, and it runs in families more than a purely environmental cause would predict.
The variant on this page for ordinary AIS risk, rs4637667, sits near GPR126 on chromosome 6q24 — one of the earliest and most consistently replicated AIS loci, first identified in the same research group's earlier genome-wide work. A follow-up study from that group, expanding to 2,109 affected subjects and 11,140 controls with additional Japanese and Chinese replication, confirmed this and previously found loci while searching for new ones — and in that same extended search identified a separate, new locus in BNC2 on chromosome 9p22.2, which is that particular paper's own headline finding. GPR126 itself encodes a receptor with roles in peripheral nerve and cartilage development, both plausible in a disease of the growing spine.
"Who develops AIS" and "whose AIS becomes severe enough to need treatment" turned out to be genetically distinct questions. A separate study by the same group, restricting its genome-wide search specifically to subjects with severe AIS — nearly 12,000 Japanese and Chinese subjects across two stages — found a third locus, rs12946942, near SOX9 and KCNJ2 on chromosome 17q24.3 (odds ratio 2.05, replicated in an independent Chinese population). Both nearby genes are already known to cause scoliosis-related conditions when mutated more severely, which makes this a biologically plausible severity locus rather than only a statistical one.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 5 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Kou I et al. 2019, Nature communications rs658839 (BCKDHB), rs7028900 (BNC2), rs17011903 (PLXNA2) — PMID:31417091
Zhu Z et al. 2015, Nature communications rs678741 (LBX1AS1), rs13398147 (PAX3) — PMID:26394188
AIS is diagnosed and tracked clinically — a physical exam (the forward-bend test), and X-rays to measure the curve's angle (the Cobb angle) — not by genotype. Treatment depends entirely on that measured severity: observation for mild curves, bracing to stop progression during remaining growth for moderate ones, and surgery for severe curves. None of the variants on this page changes that pathway.
These are population-level susceptibility findings, not a severity predictor for one person. The severity locus (SOX9/KCNJ2) came from comparing severe-AIS cases against controls, not against mild-AIS cases directly — it says severe AIS as a group differs genetically from the general population at this position, not that any one person's future curve angle can be read from their genotype.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Adolescent Idiopathic Scoliosis comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 2 of 7 linked studies with a resolved discovery ancestry.
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Adolescent Idiopathic Scoliosis. MyGeneLog™. https://www.mygenelog.com/conditions/adolescent-idiopathic-scoliosis
No. The severity-associated locus (near SOX9/KCNJ2) came from comparing people with severe AIS against the general population, not from tracking individual cases over time — it is not a validated predictor for one person's future curve. Monitoring by X-ray through the growth period is what actually tracks progression.
No — they answer different questions from different studies. rs4637667 (GPR126) relates to developing AIS at all. rs12946942 (SOX9/KCNJ2) came from a study that looked specifically at severe AIS cases, searching for what distinguishes severity, not ordinary risk.
It is not known — "idiopathic" means the cause has not been identified, after other known causes are ruled out. These loci describe genetic susceptibility found by comparing large groups of cases and controls, not an established biological mechanism for the curve itself.
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