rs112414002 (ABCC6): Multi-Tissue Expression Variant
Key takeaways
- rs112414002 is a variant in the ABCC6 gene with measurable effects on gene expression across multiple tissues
- GTEx data from 953 donors shows the alternate allele increases ABCC6 expression in seven tissue types including arteries, muscle, nerve, and brain
- The strongest expression signals are in tibial artery and skeletal muscle, with p values near 1.5e-9
- The variant also increases expression of the neighboring gene NOMO3 in sun-exposed skin
- A large UK Biobank biomarker study (n=363,228) evaluated the ABCC6 region among 1,857 loci linked to blood and urine laboratory traits
Key takeaways
- rs112414002 is a variant in the ABCC6 gene with measurable effects on gene expression across multiple tissues
- GTEx data from 953 donors shows the alternate allele increases ABCC6 expression in seven tissue types including arteries, muscle, nerve, and brain
- The strongest expression signals are in tibial artery and skeletal muscle (p values near 1.5e-9)
- The variant also increases NOMO3 expression in sun-exposed skin, affecting a second neighboring gene
- A large UK Biobank study of 35 blood and urine biomarkers (n=363,228) evaluated 1,857 loci genome-wide, including the ABCC6 region
What the research says
A genome-wide association study of 35 blood and urine laboratory biomarkers in 363,228 UK Biobank participants identified 1,857 associated loci containing 3,374 fine-mapped associations, applying Bonferroni-corrected significance thresholds (p < 5 x 10^-9) across imputed and directly genotyped variants. Expression-quantitative trait locus (eQTL) data from the GTEx project (953 donors, cis-window, FDR < 0.05) shows that the rs112414002 alternate allele is associated with increased ABCC6 transcript levels in at least seven tissues, with the strongest signals in tibial artery (p=1.6e-9) and skeletal muscle (p=1.5e-9) GTEx Portal. The same variant is independently associated with increased NOMO3 (Nodal Modulator 3) expression in sun-exposed lower-leg skin (p=1.3e-5) GTEx Portal.
Reported associations
- ABCC6 expression - aortic artery: the alternate allele associates with increased ABCC6 transcript levels in aortic artery (p=3.2e-8) GTEx Portal
- ABCC6 expression - tibial artery: increased expression in tibial artery (p=1.6e-9) GTEx Portal
- ABCC6 expression - tibial nerve: increased expression in tibial nerve (p=4.2e-8) GTEx Portal
- ABCC6 expression - frontal brain cortex (BA9): increased expression in frontal cortex region BA9 (p=7.4e-5) GTEx Portal
- ABCC6 expression - skeletal muscle: increased expression in skeletal muscle (p=1.5e-9) GTEx Portal
- ABCC6 expression - esophageal muscularis: increased expression in esophageal muscularis (p=6.0e-5) GTEx Portal
- ABCC6 expression - sun-exposed skin: increased expression in sun-exposed lower-leg skin (p=3.7e-6) GTEx Portal
- NOMO3 expression - sun-exposed skin: the alternate allele associates with increased NOMO3 transcript levels in sun-exposed lower-leg skin (p=1.3e-5) GTEx Portal
- Blood and urine biomarkers (large-scale GWAS): the ABCC6 locus was evaluated in a UK Biobank study of 35 laboratory biomarkers across 363,228 participants, which identified 1,857 loci genome-wide; the specific biomarker phenotype and effect size for this variant are not detailed in the available study excerpt
Evidence quality
The GTEx eQTL evidence is derived from 953 donors across multiple tissue types with all associations passing FDR < 0.05. The tibial artery and skeletal muscle associations are the most statistically robust (p=1.6e-9 and p=1.5e-9 respectively). The frontal cortex and esophageal muscularis associations, while passing FDR correction, have more modest p-values (7.4e-5 and 6.0e-5) and warrant cautious interpretation. The UK Biobank biomarker GWAS applied stringent Bonferroni correction (p < 5 x 10^-9) across 363,228 individuals and used LD Score regression intercepts between 0.999 and 1.137, indicating well-controlled population structure; however, the specific effect size and phenotype direction for this locus are not available in the provided text. No conflicting findings were identified across the provided data sources.
Tissue-specific expression effects
- ABCC6: the alternate allele is associated with increased expression in aortic artery, tibial artery, tibial nerve, frontal brain cortex (BA9), skeletal muscle, esophageal muscularis, and sun-exposed lower-leg skin GTEx Portal
- NOMO3: the alternate allele is associated with increased expression in sun-exposed lower-leg skin GTEx Portal
Lifestyle considerations
No lifestyle considerations on file for this variant.
Frequently asked questions
What gene is rs112414002 located in?
rs112414002 is located in ABCC6. GTEx data shows that carrying the alternate allele is associated with increased ABCC6 expression across at least seven tissue types, including arteries, skeletal muscle, tibial nerve, and brain.
What tissues are affected by rs112414002?
According to GTEx data from 953 donors, rs112414002 is associated with increased ABCC6 expression in aortic artery, tibial artery, tibial nerve, frontal brain cortex (BA9 region), skeletal muscle, esophageal muscularis, and sun-exposed lower-leg skin. It also increases NOMO3 expression in sun-exposed skin.
What is an eQTL and why does it matter for rs112414002?
An eQTL (expression quantitative trait locus) is a genetic variant that influences how much of a gene's messenger RNA is produced in a specific tissue. rs112414002 acts as an eQTL for ABCC6 in multiple tissues, meaning people with the alternate allele tend to produce more ABCC6 transcript in those tissues.
Is rs112414002 linked to any diseases?
The provided studies do not report a direct disease association for rs112414002. It appears within a large-scale UK Biobank study of blood and urine biomarkers (n=363,228), but the specific biomarker phenotype associated with this variant is not detailed in the available study data.
What is NOMO3 and why does rs112414002 affect it?
NOMO3 (Nodal Modulator 3) is a gene neighboring ABCC6. GTEx data shows rs112414002 is associated with increased NOMO3 expression specifically in sun-exposed lower-leg skin, suggesting the variant influences expression of more than one gene in this chromosomal region.