rs10503812 (EPHX2): Soluble Epoxide Hydrolase eQTL
Key takeaways
- rs10503812 is linked to increased EPHX2 gene expression in 8 different tissues, from skeletal muscle to brain to heart.
- The statistical evidence is extremely strong - p-values as low as 2.3e-116 in skeletal muscle - from 953 donors in GTEx.
- The alternative allele increases EPHX2 expression consistently, in the same direction in every tissue tested.
- No phenotype or disease associations are recorded in the provided studies for this variant.
- A liver proteomics study highlights that protein-level regulation of genes like EPHX2 often operates independently of mRNA-level changes.
Key takeaways
- rs10503812 is a genetic variant consistently associated with increased expression of the EPHX2 gene (soluble epoxide hydrolase, an enzyme that processes fatty acid epoxides) across multiple tissue types.
- The effect is strongest in skeletal muscle (p=2.3e-116) and brain cerebellar hemisphere, based on data from 953 donors in the GTEx database.
- The alternative allele increases EPHX2 expression in all 8 tissues where it has been measured, including both chambers of the heart, skin, esophagus, and cultured fibroblasts.
- No disease or phenotype associations are recorded in the provided studies for this variant.
- A liver proteomics study in 287 human samples found that protein-level expression and mRNA-level expression frequently diverge, suggesting genetic regulation of hepatic proteins like EPHX2 may extend beyond what eQTL data alone captures.
What the research says rs10503812 is an expression quantitative trait locus (eQTL) - a genetic variant statistically linked to the level of a nearby gene's expression - for EPHX2 (soluble epoxide hydrolase) across 8 distinct tissue types in data from 953 donors GTEx Portal. The effect is consistently positive in every tissue measured, meaning the alternative allele is associated with increased EPHX2 expression regardless of the tissue examined GTEx Portal. A genome-wide protein quantitative trait loci (pQTL) study in 287 normal human liver samples found that mRNA expression correlates poorly with protein levels for many hepatic genes, and that over 2,000 identified pQTL variants were not detected in previous eQTL studies - indicating that post-transcriptional mechanisms play a widespread role in regulating protein expression in the human liver.
Reported associations
- EPHX2 expression in skeletal muscle: Increased expression linked to the alternative allele (slope +0.73, p=2.3e-116) GTEx Portal
- EPHX2 expression in brain cerebellar hemisphere: Increased expression linked to the alternative allele (slope +0.72, p=7.5e-29) GTEx Portal
- EPHX2 expression in heart atrial appendage: Increased expression linked to the alternative allele (slope +0.63, p=7.9e-70) GTEx Portal
- EPHX2 expression in esophagus mucosa: Increased expression linked to the alternative allele (slope +0.63, p=2.9e-79) GTEx Portal
- EPHX2 expression in skin (non-sun-exposed): Increased expression linked to the alternative allele (slope +0.53, p=1.9e-58) GTEx Portal
- EPHX2 expression in heart left ventricle: Increased expression linked to the alternative allele (slope +0.52, p=4.5e-68) GTEx Portal
- EPHX2 expression in cultured fibroblasts: Increased expression linked to the alternative allele (slope +0.44, p=1.7e-48) GTEx Portal
- EPHX2 expression in skin (sun-exposed): Increased expression linked to the alternative allele (slope +0.40, p=4.6e-54) GTEx Portal
Evidence quality The eQTL evidence for rs10503812 is statistically robust: GTEx v11 data from 953 donors shows genome-wide significant associations in all 8 tested tissues, with p-values ranging from 7.5e-29 (brain cerebellar hemisphere) to 2.3e-116 (skeletal muscle) GTEx Portal. The uniform positive direction across every tissue tested strengthens confidence in the direction of the expression effect. No conflicting findings are present in the provided data. No GWAS phenotype associations or disease links are included in the provided studies, so the downstream functional significance of increased EPHX2 expression remains uncharacterized in this dataset. A complementary pQTL study in 287 liver samples provides relevant methodological context - specifically that protein-level and mRNA-level expression commonly diverge in liver tissue, with over 2,000 pQTL variants operating independently of known eQTL effects - but does not report a specific association for this variant in the provided text.
Tissue-specific expression effects
- EPHX2: Increased expression across all 8 tissues tested, with the strongest signal in skeletal muscle, followed by brain cerebellar hemisphere, heart atrial appendage, esophagus mucosa, skin (non-sun-exposed), heart left ventricle, cultured fibroblasts, and skin (sun-exposed) GTEx Portal
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What does the EPHX2 gene do?
EPHX2 encodes soluble epoxide hydrolase, an enzyme that processes fatty acid epoxides. rs10503812 is associated with changes in how much of this gene is expressed across multiple tissue types.
What does rs10503812 affect?
Based on GTEx data from 953 donors, rs10503812 is associated with increased EPHX2 expression in 8 tissues, including skeletal muscle, brain cerebellar hemisphere, both chambers of the heart, esophagus mucosa, skin, and cultured fibroblasts.
How strong is the evidence linking rs10503812 to EPHX2?
The GTEx eQTL data shows extremely strong statistical associations, with p-values as low as 2.3e-116 in skeletal muscle. The effect is consistent in direction across all 8 tissues studied.
Is rs10503812 linked to any disease?
The provided studies do not report any phenotype or disease associations for rs10503812. The available data describes only its association with EPHX2 gene expression levels in various tissues.
What is an eQTL and why does it matter?
An eQTL (expression quantitative trait locus) is a genetic variant statistically associated with how much a nearby gene is expressed. rs10503812 is an eQTL for EPHX2, meaning it correlates with EPHX2 expression levels across multiple tissues - though eQTL effects describe gene regulation, not direct clinical outcomes.