Expressive

rs1127102 (CNPPD1): Brain Expression eQTL Variant

Key takeaways

  • rs1127102 is linked to increased CNPPD1 expression in brain regions including the hippocampus and spinal cord.
  • The same variant is associated with reduced expression of SLC23A3, a vitamin C transporter gene, in whole blood and arterial tissue.
  • It also reduces expression of NHEJ1, a DNA repair gene, in testis tissue.
  • This variant was identified in a large proteomics study covering more than 54,000 UK Biobank participants.

Key takeaways

  • rs1127102 is linked to increased CNPPD1 expression in brain regions including the hippocampus and spinal cord.
  • The same variant is associated with reduced expression of SLC23A3, a vitamin C transporter gene, in whole blood and arterial tissue.
  • It also reduces expression of NHEJ1, a DNA repair gene, in testis tissue.
  • This variant was identified in a large proteomics study covering more than 54,000 UK Biobank participants.

What the research says rs1127102 is located near CNPPD1 and was identified in a UK Biobank proteomics study of over 54,000 samples that tested genetic associations with blood protein levels and protein ratios across 1,463 proteins. GTEx tissue expression data (953 donors, FDR<0.05) shows the alternate allele at this locus increases CNPPD1 expression across multiple brain regions, reduces SLC23A3 (a vitamin C transporter gene) in blood and vascular tissue, and reduces NHEJ1 (a gene involved in DNA repair) in testis GTEx Portal.

Reported associations

  • CNPPD1 expression in brain: Alternate allele associated with increased expression in cervical spinal cord (slope +0.65, p=9.5e-31), hippocampus (slope +0.40, p=1.0e-18), and cerebellar hemisphere (slope +0.36, p=1.6e-18) GTEx Portal.
  • SLC23A3 expression in blood and vascular tissue: Alternate allele associated with reduced expression in whole blood (slope -0.51, p=7.0e-52), aorta (slope -0.35, p=5.8e-26), tibial artery (slope -0.31, p=5.3e-32), and unexposed skin (slope -0.27, p=1.8e-28) GTEx Portal.
  • NHEJ1 expression in testis: Alternate allele associated with reduced expression in testis tissue (slope -0.36, p=1.4e-20) GTEx Portal.
  • Blood protein ratio QTL (rQTL): Identified in a UK Biobank analysis of protein ratio quantitative trait loci (rQTLs - genetic variants that influence the ratio of two protein levels in blood) covering 1,463 proteins in over 54,000 participants; the specific protein pair and effect size for this variant were not reported in the available study text.

Evidence quality The protein association evidence comes from a single large-scale study using the UK Biobank (n>54,000) with Olink Explore proximity extension assay proteomics covering 1,463 proteins, representing a substantial discovery sample. However, the specific p-value and effect size for rs1127102 on CNPPD1 protein levels are not provided in the available study text, which limits signal strength assessment for that particular association. The GTEx eQTL data (n=953 donors, FDR<0.05) provides independent tissue expression evidence with highly significant p-values ranging from approximately 1e-18 to 1e-52 across the three affected genes. No independent replication of these eQTL effects is included in the provided data; these findings should be treated as preliminary GTEx Portal.

Tissue-specific expression effects

  • CNPPD1: Increased expression in cervical spinal cord, hippocampus, and cerebellar hemisphere in alternate allele carriers GTEx Portal.
  • SLC23A3: Reduced expression in whole blood, aorta, tibial artery, and unexposed skin in alternate allele carriers GTEx Portal.
  • NHEJ1: Reduced expression in testis tissue in alternate allele carriers GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What gene is rs1127102 associated with?

rs1127102 is located near the CNPPD1 gene and influences its expression in the brain. Tissue expression data shows the alternate allele is linked to higher CNPPD1 activity in the hippocampus, cervical spinal cord, and cerebellar hemisphere.

Is rs1127102 linked to brain gene expression?

Yes. GTEx tissue expression data shows the alternate allele at rs1127102 is associated with increased CNPPD1 expression in multiple brain regions, including the hippocampus, cervical spinal cord, and cerebellar hemisphere. Whether this has any measurable effect on brain function or disease has not been established in the available research.

What is SLC23A3 and why does rs1127102 affect it?

SLC23A3 is a vitamin C transporter gene. The alternate allele at rs1127102 is associated with reduced SLC23A3 expression in whole blood, aorta, tibial artery, and unexposed skin, with the strongest effect seen in whole blood. The mechanism linking this variant to SLC23A3 regulation is not described in the available studies.

What is a protein ratio QTL (rQTL)?

A protein ratio quantitative trait locus (rQTL) is a genetic variant associated with the ratio of two protein levels in blood, rather than a single protein level. rs1127102 was identified using this approach in a UK Biobank study of over 54,000 participants measuring 1,463 proteins.

Does rs1127102 affect DNA repair genes?

Tissue expression data shows the alternate allele at rs1127102 is associated with reduced expression of NHEJ1, a gene involved in DNA repair, specifically in testis tissue. The clinical significance of this association is not established in the provided studies.