Expressive

rs112980285 (PER1): eQTL and Childhood Glioma

Key takeaways

  • rs112980285 is an eQTL that boosts the expression of nearby genes CTC1 and PFAS in skin and connective tissue cells
  • A large multi-ancestry GWAS of over 4,000 children with glioma identified the CDKN2B-AS1 region as the first genome-wide significant common genetic risk locus for pediatric astrocytoma
  • The childhood glioma association had an odds ratio of 1.273 and was consistent across 6 different genetic ancestries
  • The glioma study's lead variants differ from rs112980285, so a direct link between this variant and glioma is not yet established
  • Decreased CDKN2B expression in brain tissue was linked to childhood astrocytoma risk, suggesting a potential molecular mechanism

Key takeaways

  • rs112980285 is an eQTL that boosts the expression of nearby genes CTC1 and PFAS in skin and connective tissue cells
  • A large multi-ancestry GWAS of over 4,000 children with glioma identified the CDKN2B-AS1 region as the first genome-wide significant common genetic risk locus for pediatric astrocytoma
  • The childhood glioma association had an odds ratio of 1.273 and was consistent across 6 different genetic ancestries
  • The glioma study's lead variants differ from rs112980285, so a direct link between this variant and glioma is not yet established
  • Decreased CDKN2B expression in brain tissue was linked to childhood astrocytoma risk, suggesting a potential molecular mechanism

What the research says GTEx tissue-expression data from 953 donors shows that rs112980285 influences the activity of multiple nearby genes, with the strongest effects observed in cultured fibroblasts and skin GTEx Portal. A population-based GWAS meta-analysis of 4,069 children with glioma and 8,778 controls across multiple genetic ancestries found that common variants in CDKN2B-AS1 at 9p21.3 were significantly associated with childhood astrocytoma (OR 1.273, 95% CI 1.179-1.374, p=6.974×10^-¹^0), an association driven by low-grade tumors and consistent across all 6 ancestries tested. A transcriptome-wide analysis from the same study found that predicted decreased brain tissue expression of the CDKN2B tumor suppressor gene was significantly associated with astrocytoma (p=8.090×10^-8), suggesting a potential molecular basis for the glioma signal.

Reported associations

  • Childhood astrocytoma (low-grade): A GWAS meta-analysis identified the CDKN2B-AS1 locus at 9p21.3 as significantly associated with this subtype (OR 1.273, 95% CI 1.179-1.374, p=6.974×10^-¹^0); the association was driven by low-grade tumors (p=3.815×10^-9) and was unidirectional across 6 genetic ancestries; the study's lead variant is rs573687, not rs112980285
  • Childhood glioma (overall): The same GWAS found an association approaching genome-wide significance for glioma broadly (rs3731239, p=5.411×10^-8), with no significant signal for high-grade tumors
  • CDKN2B brain tissue expression: Predicted decreased expression of this tumor suppressor in brain tissue was significantly associated with childhood astrocytoma (p=8.090×10^-8)
  • CTC1 expression (eQTL): rs112980285 is directly associated with increased CTC1 expression in cultured fibroblasts GTEx Portal
  • PFAS expression (eQTL): rs112980285 is associated with increased PFAS expression in cultured fibroblasts GTEx Portal

Evidence quality The glioma GWAS is a well-powered meta-analysis of 4,069 pediatric cases and 8,778 controls spanning 6 genetic ancestries, with findings replicated in a separate case-control cohort. However, its primary associations are for different lead variants (rs573687 and rs3731239 at 9p21.3), and rs112980285 is not specifically named in that study. The eQTL data from GTEx (953 donors, cis-window, FDR<0.05) provides the most direct available evidence for rs112980285, demonstrating consistent expression effects across multiple genes in fibroblasts and skin. The disease-association evidence for this specific variant is therefore preliminary; the expression-level evidence is stronger but reflects gene regulation rather than clinical outcomes.

Tissue-specific expression effects

  • ENSG00000299228: Increased expression in cultured fibroblasts and in sun-exposed lower leg skin GTEx Portal
  • ENSG00000214999: Increased expression in non-sun-exposed suprapubic skin GTEx Portal
  • CTC1: Increased expression in cultured fibroblasts GTEx Portal
  • PFAS: Increased expression in cultured fibroblasts GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs112980285?

rs112980285 is a common genetic variant located near the PER1 gene. It functions as an expression QTL, meaning it influences how actively nearby genes such as CTC1 and PFAS are expressed in specific tissues including skin and cultured fibroblasts.

Is rs112980285 linked to brain tumors or childhood glioma?

The genomic region near this variant has been studied in childhood brain tumor genetics. A large multi-ancestry GWAS found that nearby variants at the CDKN2B-AS1 locus were the first confirmed common genetic risk factor for childhood astrocytoma, though rs112980285 itself was not the lead variant in that study.

What genes does rs112980285 affect?

According to GTEx data from 953 donors, the alternate allele of rs112980285 is associated with increased expression of CTC1 and PFAS in cultured fibroblasts, and with increased expression of two additional nearby genes in skin tissue.

What is CDKN2B and why does it matter for childhood astrocytoma?

CDKN2B is a tumor suppressor gene. A childhood glioma study found that lower predicted CDKN2B expression in brain tissue was significantly associated with higher astrocytoma risk, suggesting that reduced tumor suppression may contribute to this cancer in children.

How strong is the evidence linking the CDKN2B-AS1 region to childhood astrocytoma?

The evidence is robust: the GWAS analyzed over 4,000 pediatric cases across 6 genetic ancestries, independently replicated its findings, and reported an odds ratio of 1.273 with a p-value well below genome-wide significance. This applies to the CDKN2B-AS1 locus broadly, not specifically to rs112980285.