Omics · study · 2026
Integrated Transcriptomic and Functional Analysis Reveals Tissue-Specific Molecular Pathology in Adolescent Idiopathic Scoliosis
Listed in NCBI GEO
Adolescent idiopathic scoliosis (AIS), the spontaneous development of a lateral spine curvature during puberty, is the most common pediatric spine disorder, affecting ~3% of children worldwide.
Description
As the underlying etiology remains unclear, AIS is treated purely symptomatically, initially by bracing and ultimately by highly invasive, costly surgeries. Genome-wide association studies (GWAS) have identified numerous risk loci, but most are in non-coding regions, making it difficult to link them to a biological function.
To address this, we performed a multi-tissue investigation to connect genetic risk to tissue-specific molecular pathology. We conducted RNA sequencing on the primary tissues implicated in AIS—paravertebral muscle and spinal cartilage—from patients and unaffected controls. In paravertebral muscle, we identified differentially expressed genes (DEGs) enriched for pathways related to muscle structure, myogenesis, and metabolism.
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Key upregulated genes include the transcription factor EGR1 and structural components such as MYH1. In spinal cartilage, we found enrichment of genes related to TGF and FoxO signaling, as well as metabolic pathways. Notably, genes crucial for chondrocyte differentiation (e.g., SOX5 and SOX6) were significantly downregulated.
We then examined genes at known GWAS loci and found that several risk-associated genes were differentially expressed in one or both tissues. To investigate the function of non-coding variants at these loci, we identified and validated several novel enhancer elements harboring AIS risk SNPs at the BCL2, ADGRG6, and BNC2 loci. We reveal distinct pathological signatures in muscle and cartilage and lay the foundation for connecting non-coding genetic risk to the dysregulation of key developmental and structural pathways.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311180 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311180 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1368770 ncbi.nlm.nih.gov/bioproject/PRJNA1368770 ↗
project · from NCBI GEO
- PubMed 42244182 pubmed.ncbi.nlm.nih.gov/42244182 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE311180 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |