Expressive

rs11190870 (LBX1): Strongest Scoliosis Risk Variant

Key takeaways

  • rs11190870 near the LBX1 gene is the most strongly replicated genetic variant for adolescent idiopathic scoliosis (spinal curvature) identified in Japanese populations.
  • Carrying the T allele at this position gives roughly 1.5 times the odds of developing scoliosis compared to the alternative allele.
  • This variant was confirmed with extraordinarily strong statistical evidence (P = 2 x 10^-82) in a meta-analysis of nearly 80,000 Japanese individuals.
  • The variant affects LBX1-AS1 gene expression differently across tissues, increasing it in testis and decreasing it in skin.
  • All large studies were conducted in Japanese populations, and the variant's effects in other ethnic groups are not fully characterized in the available data.

Key takeaways

  • rs11190870 near the LBX1 gene on chromosome 10q24.31 is the most strongly replicated genetic variant for adolescent idiopathic scoliosis (AIS, a sideways spinal curvature) identified in Japanese populations.
  • The T (risk) allele is found in approximately 66% of AIS cases versus 56% of controls and confers roughly 1.5 times the odds of developing AIS.
  • This locus was confirmed with exceptionally strong statistical evidence (OR 1.52, P = 2.01 x 10^-82) in a meta-analysis of nearly 80,000 Japanese individuals.
  • The variant affects expression of the nearby LBX1-AS1 gene in opposite directions depending on tissue, increasing it in testis and decreasing it in skin.
  • All large discovery and replication studies were conducted in Japanese populations; generalizability to other ethnic groups is not established in the available data.

What the research says rs11190870, located at chromosome 10q24.31 near LBX1 (encoding ladybird homeobox 1, a transcription factor that helps switch other genes on or off during development) and overlapping the long non-coding RNA genes LINC01514 and LBX1-AS1 (RNA molecules that do not produce protein but may regulate gene activity), was first identified as an AIS susceptibility locus in a GWAS of 1,376 Japanese females with AIS and 11,297 female controls, yielding a combined P-value of 1.24 x 10^-19 and an odds ratio of 1.56 PMID 22751497. A 2019 meta-analysis of three GWASs across 79,211 Japanese individuals confirmed the locus as the strongest known AIS signal (OR 1.52, 95% CI 1.46-1.59, P = 2.01 x 10^-82; T allele frequency 66% in cases versus 56% in controls), and found that 20 confirmed AIS loci together explain 4.6% of the phenotypic variance (the total measurable variation in the trait across the population) of AIS PMID 31551428. That same meta-analysis identified significant genetic correlations between AIS genetic architecture and both body mass index and uric acid levels, suggesting partially overlapping genetic pathways PMID 31551428.

Reported associations

  • Adolescent idiopathic scoliosis (discovery, Japanese females): The T allele is associated with approximately 1.56-fold increased odds of AIS (combined P = 1.24 x 10^-19; n = 1,376 cases and 11,297 controls). PMID 22751497
  • Adolescent idiopathic scoliosis (meta-analysis confirmation, Japanese): Confirmed as the single strongest genome-wide signal across 20 AIS loci (OR = 1.52, 95% CI 1.46-1.59, P = 2.01 x 10^-82; n = 79,211; T allele in 66% of cases versus 56% of controls). PMID 31551428

Evidence quality The association between this variant and AIS is among the most robustly evidenced findings in AIS genetics. The original discovery study (1,376 cases, 11,297 controls) achieved a combined P = 1.24 x 10^-19 PMID 22751497, and the subsequent meta-analysis of 79,211 individuals elevated this to P = 2.01 x 10^-82, the single strongest signal across all 20 identified AIS loci; the variant was directly genotyped rather than imputed in that analysis, supporting data quality PMID 31551428. A separate multi-ethnic meta-analysis of 7,956 cases and 88,459 controls from three ancestral groups confirmed the complex genetic architecture of AIS but focused on newly identified loci (in the CDH13, ABO, and SOX6 genes) rather than replicating this specific variant PMID 31665284. No conflicting findings for rs11190870 are reported across the provided studies; however, all primary discovery and replication evidence is from Japanese cohorts, and heritability enrichment analyses suggest that AIS etiology involves multiple cell-type groups, implying heterogeneous biological pathways PMID 31551428.

Tissue-specific expression effects

  • LBX1-AS1: The ALT allele is associated with increased expression in testis and reduced expression in both non-sun-exposed suprapubic skin and sun-exposed lower-leg skin; the opposite direction of effect between testis and skin suggests tissue-specific regulatory roles for this locus and should be read as a mechanistic observation rather than a clinical outcome. GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11190870?

rs11190870 is a genetic variant on chromosome 10 near the LBX1 gene. It is the most statistically significant known genetic marker for adolescent idiopathic scoliosis identified in Japanese populations, with the risk allele found in about 66% of affected individuals versus 56% of controls.

What does the LBX1 gene do?

LBX1 encodes a protein called ladybird homeobox 1, a transcription factor that helps switch other genes on or off during development. Variants near this gene have been consistently linked to adolescent spinal curvature in multiple large genetic studies.

Is rs11190870 linked to scoliosis?

Yes, the T allele of rs11190870 is associated with about 1.5 times the odds of developing adolescent idiopathic scoliosis. This has been replicated in studies involving tens of thousands of individuals from Japanese populations.

What is adolescent idiopathic scoliosis?

Adolescent idiopathic scoliosis is the most common spinal deformity in children, involving a sideways curvature of the spine exceeding 10 degrees. It affects roughly 2-3% of school-age children worldwide and is thought to involve both genetic and environmental factors, though the genetic contributors are only partially understood.

Does rs11190870 affect gene expression?

Yes, GTEx data show that this variant influences expression of LBX1-AS1 in a tissue-specific way. The effect increases expression in testis but decreases it in skin tissue, suggesting different regulatory roles depending on tissue type.